View details for Web of Science ID 000289035600128, View details for Web of Science ID 000289035600373. We identified a 2.2 kilobase ncRNA residing in the HOXC locus, termed HOTAIR, which represses transcription in trans across 40 kilobases of the HOXD locus. Conversely, pharmacological and molecular inhibition of the PDGF signalling pathway ameliorated the arrhythmic phenotypes of mutant iPSC-CMs in vitro. Within epidermal tissue, JMJD3 depletion blocked differentiation, while active JMJD3 dominantly induced it. Lee, C., Qu, K., Webster, D., Kretz, M., MAH, A., Ungewickell, A., Armstrong, R., Weng, W., Kim, Y., Chang, H., Khavari, P. Long noncoding RNA programs active chromatin domain to coordinate homeotic gene expression, Long Intergenic Noncoding RNAs: New Links in Cancer Progression, Noncoding RNA Landmarks of Pluripotency and Reprogramming, G1 arrest and differentiation can occur independently of Rb family function. Diseases associated with ID2 include Retinoblastoma and Ewing Sarcoma.Among its related pathways are Signaling by NTRKs and Nuclear Events (kinase and transcription factor activation).Gene Ontology (GO) annotations related to this gene include protein dimerization activity and transmembrane The entire experimental protocol takes 5 d to complete, and sequencing and data analysis take an additional 6-8 d. PARS was developed using the yeast genome as proof of principle, but its approach should be applicable to probing RNA structures from different transcriptomes and structural dynamics under diverse solution conditions. The site is secure. Recent studies in several different systems suggest that not only may the rate of aging be modified by environmental and genetic factors, but also that the aging clock can be reversed, restoring characteristics of youthfulness to aged cells and tissues. How are these site-specific differences specified during development, maintained in adult homeostasis, and potentially perturbed by disease processes? Finally, transcription factor binding analysis suggests that lncRNAs are directly regulating cardiac gene expression during development.-We provide a systematic analysis of lncRNA control of heart development that gives clues to the roles that specific lncRNAs play in fetal and adult hearts. High-throughput sequencing targeting the 3' end of polyadenylated transcripts in archived tumors from 24 additional patients with tumor-stage CTCL confirmed the differential expression of SC-associated lncRNAs and SeCATs in CTCL. lentivirus, AAV, adenovirus), Custom and pre-made DNA vectors for HOPX (ie. In this review, we discuss the use of genomic technologies to characterize chromatin structure in vivo, with a focus on data from budding yeast and humans. During both embryonic development and adult tissue regeneration, changes in chromatin structure driven by master transcription factors lead to stimulus-responsive transcriptional programs. Hence, BBL treatment can restore gene expression pattern of photoaged and intrinsically aged human skin to resemble young skin. Cohesin HiChIP10 visualizations of chromosome conformation show that p63 and the morphogens contribute to dynamic long-range chromatin interactions, as illustrated by TFAP2C regulation11. Satb1 integrates DNA binding site geometry and torsional stress to differentially target nucleosome-dense regions. Those proteins showed strong enrichment for common human RNA binding domains such as RRM, RBD, as well as K homology and CCCH type zinc finger motifs. The ability to tether two distinct complexes enables RNA-mediated assembly of PRC2 and LSD1 and coordinates targeting of PRC2 and LSD1 to chromatin for coupled histone H3 lysine 27 methylation and lysine 4 demethylation. PubMed PMID:22484976. The Daxx-ASK1 connection completes a signaling pathway from a cell surface death receptor to kinase cascades that modulate nuclear transcription factors. Alterations in the primary structure, secondary structure, and expression levels of lncRNAs as well as their cognate RNA-binding proteins underlie diseases ranging from neurodegeneration to cancer. The most notable feature of the global gene-expression pattern observed in AE skin was a reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. SCENICTranscription factor TF Studying cancer metabolism gives insight into tumorigenic survival mechanisms and susceptibilities. Fas activation induced Daxx to interact with ASK1, which consequently relieved an inhibitory intramolecular interaction between the amino- and carboxyl-termini of ASK1, activating its kinase activity. This level of organization is essential for the correct execution of multiple processes in the cell, ranging from cell signaling to assembly of structures such as the ribosomes. These findings suggest a key role for transcription and CTCF in the formation of TADs in the context of the Xi chromosome in neural progenitors. The DNA-associated protein encoded by this gene is a member of the paired family of homeobox proteins localized to the nucleus. Thus, DDX3 interacts extensively with RNA and ribosomal machinery to help remodel the translation landscape in response to stress, while cancer-related DDX3 variants adapt this response to selectively preserve translation. These studies also produced new FACS methods for purifying DE from nontransgenic mice and mouse ES cell cultures. Finally, transcription factor binding analysis suggests that lncRNAs are directly regulating cardiac gene expression during development.-We provide a systematic analysis of lncRNA control of heart development that gives clues to the roles that specific lncRNAs play in fetal and adult hearts. Our study demonstrates the unexpected dependency of p63 on morphogenetic signaling and provides novel insights into how a master regulator can specify diverse transcriptional programs based on the chromatin landscape induced by exposure to specific morphogens. Th2-like Treg cells showed increased intra-chromosomal interactions in the Th2 locus, leading to type 2 cytokine production. Here, we demonstrate that terminally differentiated hepatocytes can be directly converted into functional iN cells. The SJL/J-derived locus confers higher lncRNA expression, increased interferon- (IFN-) abundance in activated CD8(+) T cells, increased Theiler's virus persistence, and decreased Salmonella enterica pathogenesis. EDEM1 associates with lifespan in animal models, although not humans. Furthermore, the dominant-negative effect of the G228W variant was exerted through recruitment of WT Aire away from active sites of transcription in the nucleus of medullary thymic epithelial cells in vivo. APEX-seq in nine distinct subcellular locales produced a nanometer-resolution spatial map of the human transcriptome as a resource, revealing extensive patterns of localization for diverse RNA classes and transcript isoforms. The lincRNA termed HOTAIR is increased in expression in primary breast tumours and metastases, and HOTAIR expression level in primary tumours is a powerful predictor of eventual metastasis and death. Yang, Y. W., Flynn, R. A., Chen, Y., Qu, K., Wan, B., Wang, K. C., Lei, M., Chang, H. Y. Prevents SRF-dependent transcription either by inhibiting SRF binding to DNA or by recruiting histone deacetylase (HDAC) proteins that prevent transcription by SRF. Here we map Sirt6 occupancy on mouse promoters genome-wide and show that Sirt6 occupancy is highly dynamic in response to TNF-. ChIRP-ms is robust across a wide range of expression level, from abundant housekeeping RNAs (e.g., spliceosomal U RNAs) to relatively lowly expressed RNAs (e.g., Xist). Thousands of long noncoding RNAs (lncRNAs) have been discovered, but their functional characterization has been slowed by a limited set of research tools. Just as chromatin immunoprecipitation followed by microarray or deep sequencing (ChIP-chip or ChIP-seq, respectively) has greatly improved our understanding of protein-DNA interactions on a genomic scale, here we illustrate a recently published strategy to map long RNA occupancy genome-wide at high resolution (17). Littlepage, L. E., Adler, A. S., Kouros-Mehr, H., Huang, G., Chou, J., Krig, S. R., Griffith, O. L., Korkola, J. E., Qu, K., Lawson, D. A., Xue, Q., Sternlicht, M. D., Dijkgraaf, G. J., Yaswen, P., Rugo, H. S., Sweeney, C. A., Collins, C. C., Gray, J. W., Chang, H. Y., Werb, Z. Uncovering the role of genomic "dark matter" in human disease, Identification of genes promoting exceptional skin youthfulness. We found that MYC induces DNA double-strand breaks (DSBs) independent of ROS production in murine lymphocytes in vivo as well as in normal human foreskin fibroblasts (NHFs) in vitro in normal (10%) serum, as measured by gammaH2AX staining. A., Chang, H. Y. CSN5 isopeptidase activity links COP9 signalosome activation to breast cancer progression. By probing yeast RNA structures at different temperatures, we obtained relative melting temperatures (Tm) for RNA structures in over 4000 transcripts. Accordingly, mTOR inhibition suppressed fibroblast recruitment and proliferation of HOXB13-expressing ER+ breast cancer cells and tumor xenografts, alone or in combination with TAM. Recent efforts have been focused on developing reagents that modify RNA as a function of RNA 2' hydroxyl group reactivity. Age-specific NF-kappaB blockade and orthogonal cell cycle interventions revealed that NF-kappaB controls cell cycle exit and gene expression signature of aging in parallel but not sequential pathways. The Omni-ATAC protocol enables the interrogation of personal regulomes in tissue context and translational studies. View details for DOI 10.1016/S0076-6879(06)20010-7. 9d. Consistent with this notion, lncRNAs can function as modular scaffolds to specify higher-order organization in RNP complexes and in chromatin states. Our results demonstrate the ability of the enhancer connectome to nominate functionally-relevant candidates from GWAS-identified variants, representing a powerful tool to guide future studies into the genomic regulatory mechanisms underlying dermatologic diseases. 8600 Rockville Pike Restoration of proper organ function often requires restoring homeostatic gene regulation. 2011), Oligodendrocyte progenitor cells(Najm FJ et. Inducible genetic blockade of NF-kappaB for 2 wk in the epidermis of chronologically aged mice reverted the tissue characteristics and global gene expression programs to those of young mice. Here we review emerging RNA-centric methods to interrogate the intrinsic structure of lncRNAs as well as their genomic localization and biochemical partners. The exosome complex recognizes unpaired bases during heat shock to degrade these RNAs, coupling intrinsic structural stabilities to gene regulation. Chen, L. n., Roake, C. M., Freund, A. n., Batista, P. J., Tian, S. n., Yin, Y. We applied Assay of Transposase Accessible Chromatin with sequencing (ATAC-seq) to map chromatin accessibility in primary CD4+ T cells isolated from standard blood draws of 12 healthy volunteers over time, from cancer patients, and during T cell activation. More than half of Sirt6 target genes are only revealed upon stress-signaling. The six SNPs were interrogated by MassARRAY in a replication group (n=436) with confirmation of rs6975107, an intronic region of KCND2 (potassium voltage-gated channel, Shal-related family member 2) (Pgenotype=0.023). Co-addiction to IRF4 and SPIB in ABC-DLBCL, The unique molecular signature of cortical tissue injury in Multiple Sclerosis. p63 distally closes chromatin accessibility and promotes accumulation of H3K27me3 (trimethylated histone H3 lysine 27). Eukaryotic genomes are packaged into chromatin, where diverse histone modifications can demarcate chromatin domains that facilitate or block gene expression. Hey2, the human homologue of the zebrafish gene gridlock, was selectively expressed in arterial ECs and induced the expression of several arterial-specific genes. View details for DOI 10.1016/j.stem.2014.09.019. Cho, S. W., Xu, J., Sun, R., Mumbach, M. R., Carter, A. C., Chen, Y. G., Yost, K. E., Kim, J., He, J., Nevins, S. A., Chin, S., Caldas, C., Liu, S. J., Horlbeck, M. A., Lim, D. A., Weissman, J. S., Curtis, C., Chang, H. Y. STAU1-deficient tissue recapitulated the impaired differentiation seen with TINCR depletion. Careers. An emerging theme from multiple model systems is that lncRNAs form extensive networks of ribonucleoprotein (RNP) complexes with numerous chromatin regulators and then target these enzymatic activities to appropriate locations in the genome. Here, an enhancer-like lncRNA termed NeST (nettoie Salmonella pas Theiler's [cleanup Salmonella not Theiler's]) is shown to be causal for all phenotypes conferred by murine viral susceptibility locus Tmevp3. The full data set is available at http://microarray-pubs.stanford.edu/eczema. View details for DOI 10.1126/science.aav1898, View details for DOI 10.1016/j.xpro.2021.100477. 2011), Oligodendrocyte-like cells(Sundberg M et. A subsequent study revealed that HOTAIR is overexpressed in approximately one quarter of human breast cancers, directing PRC2 to approximately 800 ectopic sites in the genome, which leads to histone H3 lysine 27 trimethylation and changes in gene expression[4]. This gene encodes a member of the basic helix-loop-helix (BHLH) family of transcription factors. elegans genome edited models for ASCL1, starting at $3,250. Combinations of twenty-eight imaging traits can reconstruct 78% of the global gene expression profiles, revealing cell proliferation, liver synthetic function, and patient prognosis. This gene is overexpressed in Skin (13.0), Oral epithelium (11.8), Esophagus (6.6), and Heart (6.6). Using a mouse hybrid F1 system, we found that monoallelic DNA accessibility across autosomes was pervasive, developmentally programmed and composed of several patterns. We conclude that while multiple SHAPE technologies are effective at measuring purified RNAs in vitro, acylimidazole reagents NAI and NAI-N3 give markedly greater signals with lower background than 1M7 for in vivo measurement of the RNA structurome. viral and non-viral vectors), Virus packaging for HOPX shRNA knockdown vectors (ie. This gene was present in the common ancestor of animals. Unlike most other human ERVs, HERVK retained multiple copies of intact open reading frames encoding retroviral proteins. SeqFold is able to incorporate diverse types of RNA structure profiling data, including parallel analysis of RNA structure (PARS), selective 2'-hydroxyl acylation analyzed by primer extension sequencing (SHAPE-Seq), fragmentation sequencing (FragSeq) data generated by deep sequencing, and conventional SHAPE data. Here we show that the mammalian Bgcn homolog YTHDC2 facilitates a clean switch from mitosis to meiosis in mouse germ cells, revealing a conserved role for YTHDC2 in this critical cell fate transition. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. HLF (HLF Transcription Factor, PAR BZIP Family Member) is a Protein Coding gene. Leukemia cutis may clinically mimic many inflammatory dermatoses. Over 1,900 transcribed single nucleotide variants (approximately 15% of all transcribed single nucleotide variants) alter local RNA structure. A., Zhou, W. n., Silva, T. C., Groeneveld, C. n., Wong, C. K., Cho, S. W., Satpathy, A. T., Mumbach, M. R., Hoadley, K. A., Robertson, A. G., Sheffield, N. C., Felau, I. n., Castro, M. A., Berman, B. P., Staudt, L. M., Zenklusen, J. C., Laird, P. W., Curtis, C. n., Greenleaf, W. J., Chang, H. Y. View details for Web of Science ID 000302866900385. Hox genes encode transcription factors that specify embryonic positional identity in cells and guide tissue differentiation. INHBB (Inhibin Subunit Beta B) is a Protein Coding gene. As a result, they affect several stages of gene regulation, including chromatin modification, mRNA biogenesis, and protein signaling. Understanding these technologies, including their advantages and caveats, and developing them in the future will be essential to progress from description to comprehension of the myriad roles of lncRNAs. Our findings characterize the SS transcriptome and support recent reports that implicate lncRNA dysregulation in human malignancies. Here, we show that the lincRNA HOTAIR serves as a scaffold for at least two distinct histone modification complexes. View details for DOI 10.1038/s41591-019-0522-3. FOIA Based on recent X-ray structural information, six site-directed mutants of human cyclophilin A (hCyPA) involving residues in the putative active site--H54, R55, F60, Q111, F113, and H126--have been constructed, overexpressed, and purified from Escherichia coli to homogeneity. Wang, P., McKnight, K. D., Wong, D. J., Rodriguez, R. T., Sugiyama, T., Gu, X., Ghodasara, A., Qu, K., Chang, H. Y., Kim, S. K. The Transcription Factor ZNF217 Is a Prognostic Biomarker and Therapeutic Target during Breast Cancer Progression. Experimental evidence suggests that in cancer, they can influence Polycomb Repressive Complexes (PRC) to retarget to an occupancy pattern resembling that of the embryonic state. Diseases associated with IGFBP7 include Retinal Arterial Macroaneurysm With Supravalvular Pulmonic Stenosis and Diabetic Angiopathy.Among its related pathways are Cellular responses to stimuli and Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Here we show that calcineurin, a protein phosphatase enriched in growth cones that is dependent on calcium ions and calmodulin, functions in neurite outgrowth and directed filopodial motility in cultured chick dorsal root ganglia neurons. VIDEO ABSTRACT. Here we have used gene expression profiling by microarray analysis to identify gene expression profiles that can help to predict local recurrence in individual patients.By using previously established gene expression profiles with proven value in predicting metastasis-free and overall survival (wound-response signature, 70-gene prognosis profile and hypoxia-induced profile) and training towards an optimal prediction of local recurrences in a training series, we establish a classifier for local recurrence after breast-conserving therapy.Validation of the different gene lists shows that the wound-response signature is able to separate patients with a high (29%) or low (5%) risk of a local recurrence at 10 years (sensitivity 87.5%, specificity 75%). Fas is a cell surface death receptor that regulates peripheral tolerance and lymphoid homeostasis. Revealing long noncoding RNA architecture and functions using domain-specific chromatin isolation by RNA purification. Efficient DNA binding requires dimerization with another bHLH protein. 2012 Aug; 29 (6) :615-24. Telomerase expression plays a role in cellular senescence, as it is MYC overexpression is thought to initiate tumorigenesis by inducing cellular proliferation and growth and to be restrained from causing tumorigenesis by inducing cell cycle arrest, cellular senescence, and/or apoptosis. A., Chang, H. Y., van de Vijver, M. J. Deletional tolerance mediated by extrathymic Aire-expressing cells. knockout, knockin, CRISPRa, CRISPRi), VectorBuilder Virus packaging for HOPX CRISPR vectors (ie. Diseases associated with ETV5 include Acoustic Neuroma and Charcot-Marie-Tooth Disease, Axonal, Type 2Dd.Among its related pathways are IL12-mediated signaling events and IL12 signaling mediated by STAT4.Gene Ontology (GO) annotations related to this gene include DNA-binding This study identified a novel set of candidate skin youthfulness genes demonstrating differences between SY and non-SY group, including pleckstrin homology like domain family A member 1 (PHLDA1) (p = 2.4x10-5), a follicle stem cell marker, and hyaluronan synthase 2-anti-sense 1 (HAS2-AS1) (p = 0.00105), a non-coding RNA that is part of the hyaluronan synthesis pathway. Because Pax8 is a thyroid specific transcription factor and because its DNA binding domain is fused to the c-terminal domains of PPAR other ETS family members including ETV1 , ETV4 [149, 150] and ETV5 also contribute to gene fusions in prostate cancer, albeit at a Qu, K., Garamszegi, S., Wu, F., Thorvaldsdottir, H., Liefeld, T., Ocana, M., Borges-Rivera, D., Pochet, N., Robinson, J. T., Demchak, B., Hull, T., Ben-Artzi, G., Blankenberg, D., Barber, G. P., Lee, B. T., Kuhn, R. M., Nekrutenko, A., Segal, E., Ideker, T., Reich, M., Regev, A., Chang, H. Y., Mesirov, J. P. Transcriptome-wide interrogation of RNA secondary structure in living cells with icSHAPE. The DNA-associated protein encoded by this gene is a member of the paired family of homeobox proteins localized to the nucleus. Buenrostro, J. D., Corces, M., Lareau, C. A., Wu, B., Schep, A. N., Aryee, M. J., Majeti, R., Chang, H. Y., Greenleaf, W. J. Diseases associated with SFRP2 include Colorectal Cancer and Esophageal Basaloid Squamous Cell Carcinoma.Among its related pathways are ncRNAs involved in Wnt signaling in hepatocellular carcinoma and Signaling by WNT.Gene Ontology (GO) annotations related to this gene include Su, M. A., Giang, K., Zumer, K., Jiang, H., Oven, I., Rinn, J. L., DeVoss, J. J., Johannes, K. P., Lu, W., Gardner, J., Chang, A., Bubulya, P., Chang, H. Y., Peterlin, B. M., Anderson, M. S. Module map of stem cell genes guides creation of epithelial cancer stem cells. However, the expansion of T cell clones did not derive from pre-existing tumor-infiltrating T lymphocytes; instead, the expanded clones consisted of novel clonotypes that had not previously been observed in the same tumor. Long Noncoding RNAs: At the Intersection of Cancer and Chromatin Biology. Widely expressed. Chromatin immunoprecipitation (ChIP) is an assay for interrogating protein-DNA interactions that is increasingly being used for drug target discovery and screening applications. Reciprocal interactions between mesenchymal and epithelial cells are known to play a critical role in orchestrating the development and morphogenesis of tissues and organs, but the roles played by specific stromal cells in controlling the design and function of tissues remain poorly understood. The eigenstrat method showed no stratification. In addition, hSSC-derived stroma can maintain human hematopoietic stem cells (hHSCs) in serum-free culture conditions. The XIST RNA is large and complex, exemplifying the unique challenges associated with the structural and functional analysis of lncRNAs. Targeted disruption of hotair leads to homeotic transformation and gene derepression. Telomerase expression plays a role in cellular senescence, as it is Phenotype-based relationships between genes and organs from Gene ORGANizer, 57% of all genes are more intolerant (likely to be disease-causing), 51.04% of all genes are more intolerant (likely to be disease-causing), Polymorphic Variants from UniProtKB/Swiss-Prot, UniProtKB/Swiss-Prot and Since their introduction to the US market, atypical antipsychotic drugs, such as olanzapine, have been widely prescribed for the management of psychosis and have increasingly been used in dermatologic settings for the treatment of psychogenic dermatoses. Genes induced in the fibroblast serum-response program are expressed in tumors by the tumor cells themselves, by tumor-associated fibroblasts, or both. NCBI Functional elements and These results suggest dChIRP can reveal lncRNA architecture and function with high precision and sensitivity. 2010), Lateral Ganglionic Eminence progenitors(Ma L et. Genome conformation is central to gene control but challenging to interrogate. c-Myc-enhanced tumor initiation is cell-autonomous and independent of genomic instability. View details for DOI 10.1067/mjd.2003.233, View details for Web of Science ID 000184135000021. Using genetically engineered mice, we found that Rai1 preferentially occupies DNA regions near active promoters and promotes the expression of a group of genes involved in circuit assembly and neuronal communication. Nuyten, D. S., Kreike, B., Hart, A. All rights reserved. Taken together, our results establish a function for HOXB13 in TAM resistance through direct suppression of ER and they identify the IL-6 pathways as mediator of disease progression and recurrence. PharmGKB Summary , Kretz, M., Siprashvili, Z., Chu, C., Webster, D. E., Zehnder, A., Qu, K., Lee, C. S., Flockhart, R. J., Groff, A. F., Chow, J., Johnston, D., Kim, G. E., Spitale, R. C., Flynn, R. A., Zheng, G. X., Aiyer, S., Raj, A., Rinn, J. L., Chang, H. Y., Khavari, P. A. In all inhibition assays with [32P]casein or [Ser(32P)15]RII, the concentration of calcineurin required for measurable phosphatase activity is such that these complexes behave as tight-binding inhibitors of calcineurin, and steady-state kinetics cannot be used to assess inhibition patterns or Ki values. The process of cancer metastasis involves a series of sequential and complex steps. Lee, J. n., Termglinchan, V. n., Diecke, S. n., Itzhaki, I. n., Lam, C. K., Garg, P. n., Lau, E. n., Greenhaw, M. n., Seeger, T. n., Wu, H. n., Zhang, J. Here we review evidence showing that lncRNAs exert critical functions in adult tissue stem cells, including skin, brain, and muscle, as well as in developmental patterning and pluripotency. In addition, the expression of a large number of Aire-regulated thymic antigens was partially inhibited in these animals, demonstrating the importance of quantitative changes in thymic antigen expression in determining organ-specific autoimmunity. Control of somatic tissue differentiation by the long non-coding RNA TINCR. Modular domains of long non-coding RNAs can serve as scaffolds to bring distant regions of the linear genome into spatial proximity. Hearing loss, sensorineural; Sensorineural deafness; Sensorineural hearing loss, Abnormality of the peripheral nervous system. Divergent, antisense, and enhancer-like intergenic noncoding RNAs can either activate or repress gene expression by altering histone H3 lysine 4 methylation. SFRP2 (Secreted Frizzled Related Protein 2) is a Protein Coding gene. A new class of transcripts, long noncoding RNAs (lncRNAs), has been recently found to be pervasively transcribed in the genome. MMP1 (Matrix Metallopeptidase 1) is a Protein Coding gene. Rubin, A. J., Barajas, B. C., Furlan-Magaril, M. n., Lopez-Pajares, V. n., Mumbach, M. R., Howard, I. n., Kim, D. S., Boxer, L. D., Cairns, J. n., Spivakov, M. n., Wingett, S. W., Shi, M. n., Zhao, Z. n., Greenleaf, W. J., Kundaje, A. n., Snyder, M. n., Chang, H. Y., Fraser, P. n., Khavari, P. A. TINCR-mRNA interaction occurs through a 25-nucleotide 'TINCR box' motif that is strongly enriched in interacting mRNAs and required for TINCR binding. Biological response to low dose of alpha-particles in a human 3-dimensional skin model, in 1 and 16h after exposure to ionizing radiation. Koh, A. S., Miller, E. L., Buenrostro, J. D., Moskowitz, D. M., Wang, J., Greenleaf, W. J., Chang, H. Y., Crabtree, G. R. m(6)A mRNA methylation sustains Treg suppressive functions. A., Verhaak, R. G., Hu, M., Furnari, F. B., Chang, H. Y., Ren, B., Bafna, V., Mischel, P. S. Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion. Rapicavoli, N. A., Qu, K., Zhang, J., Mikhail, M., Laberge, R., Chang, H. Y. Detailed gene expression maps have now shown the diversity and distinctiveness in gene expression programs associated with stemness in embryonic and adult stem cells. Further, ING4 facilitates apoptosis in response to genotoxic stress and inhibits anchorage-independent cell growth, and these functions depend on ING4 interactions with H3K4me3. Prevents SRF-dependent transcription either by inhibiting SRF binding to DNA or by recruiting histone deacetylase (HDAC) proteins that prevent transcription by SRF. Overall, this work provides a framework for integrative exploration of complex regulatory dynamics in a primary human tissue at single-cell resolution. The transcription factor PBX3 promotes tumor cell growth through transcriptional suppression of the tumor suppressor p53. Recent advances in high throughput sequencing enabled the development of methods for probing RNA structures on a transcriptome-wide scale-termed the RNA structurome. DEAD-box RNA helicases are vital for the regulation of various aspects of the RNA life cycle, but the molecular underpinnings of their involvement, particularly in mammalian cells, remain poorly understood. Furthermore, altered patterns of facultative escape genes indifferent neural progenitor clones are associated with the presence of different TAD-like structures after XCI. Here, we apply H3K27ac HiChIP high-resolution contact maps, generated from primary human T-cell subsets (CD4+ Naive, TH17, and Treg), to 21 dermatologic conditions associated with single nucleotide polymorphisms (SNPs) from 106 genome-wide association studies (GWAS). Long noncoding RNAs (lncRNAs) are important regulators of cell fate, yet little is known about mechanisms controlling lncRNA expression. Cho, S., Xu, J., Sun, R., Mumbach, M. R., Carter, A. C., Chen, Y., Yost, K. E., Kim, J., He, J., Nevins, S. A., Chin, S., Caldas, C., Liu, S., Horlbec, M. A., Lim, D. A., Weissman, J. S., Curtis, C., Chang, H. Y. ATAC Primer Tool for targeted analysis of accessible chromatin. View details for DOI 10.1182/blood-2012-04-423061. lncRNAs exhibit several distinctive features that confer unique regulatory functions, including exquisite cell- and tissue-specific expression and the capacity to transduce higher-order spatial information. 9d). The Supplementary Information to this Amendment contains the corrected and reanalysed Extended Data Fig. Selective expression of the programmed death-ligand 1 (PD-L1) was observed on CD44+ cells compared to CD44- cells and was associated with constitutive phosphorylation of STAT3 on CD44+ cells. Gene set analysis was performed using Genomica open-access software. Quantitative analysis of RNA-protein interactions on a massively parallel array reveals biophysical and evolutionary landscapes. Recent advances have greatly increased our understanding of the epigenetic mechanisms that ensure the faithful expression of Hox genes in adult cells and which involve the interplay of histone methylation, demethylation and intergenic transcription of long non-coding RNAs. miR-204: a novel therapeutic target, Transcriptome analysis of highly metastatic cell line, The Leukemia-associated Mllt10/Af10- Dot1l, dedicated b-catenin coactivators essential for intestinal homeostasis, A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma. Systemic sclerosis (SSc) is an autoimmune disease in which the tyrosine kinases platelet-derived growth factor receptor (PDGFR) and Abl are hypothesized to contribute to the fibrosis and vasculopathy of the skin and internal organs. An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma. Chen, L., Roake, C. M., Freund, A., Batista, P. J., Tian, S., Yin, Y. How do cells know where they are located in the body, and how do they remember this information?We discovered that one class of skin cells, the fibroblasts, encode the positional identity of skin via specific markings on their chromatin, the DNA-protein complex where genes reside. Wapinski, O. L., Vierbuchen, T., Qu, K., Lee, Q. Y., Chanda, S., Fuentes, D. R., Giresi, P. G., Ng, Y. H., Marro, S., Neff, N. F., Drechsel, D., Martynoga, B., Castro, D. S., Webb, A. E., Suedhof, T. C., Brunet, A., Guillemot, F., Chang, H. Y., Wernig, M. Augmenting Endogenous Wnt Signaling Improves Skin Wound Healing. We show that autoimmune eye disease in aire-deficient mice develops as a result of loss of thymic expression of a single eye antigen, interphotoreceptor retinoid-binding protein (IRBP). Its overexpression in a zebrafish melanoma model suppresses cancer formation, while its inactivation accelerates tumor onset invivo. These data reveal genetic risk loci of cancer predisposition as active DNA regulatory elements in cancer, identify gene-regulatory interactions underlying cancer immune evasion, and pinpoint noncoding mutations that drive enhancer activation and may affect patient survival. In the nucleolus, DDX21 occupies the transcribed rDNA locus, directly contacts both rRNA and snoRNAs, and promotes rRNA transcription, processing and modification. View details for DOI 10.1371/journal.pone.0004017, View details for Web of Science ID 000265463000012, View details for PubMedCentralID PMC2603322. Defining Cell Fate And Embryonic Genome Activation By Global Single-Cell cDNA Analysis of Blastomeres From 5-to 8-Cell Human Embryos. At the molecular level, we demonstrate that impaired rRNA synthesis elicits a DNA damage response, and that rDNA damage results in tissue-selective and dosage-dependent effects on craniofacial development. Paralleling the diversity of genetic and protein activities, pathologic human tissues also exhibit diverse radiographic features. View details for Web of Science ID 000276635000045, View details for PubMedCentralID PMC3049919. We found that a large number of genes of ZNF transcription factors were bound by both KAP1 and H3me3K9 in normal and cancer cells. View details for DOI 10.1098/rstb.2016.0356, View details for Web of Science ID 000411682500003. Transcription Factor Targeted Genes and A., Qu, K., Georgiev, P., Chu, C., Akhtar, A., Chang, H. Y. Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and assists in chaperone-mediated protein refolding (PubMed:27708256). View details for Web of Science ID 000380856600034, View details for PubMedCentralID PMC5443622. official website and that any information you provide is encrypted al. Finally, the decreased immunogenicity of CD44+ cells was partially reversed by antibody blockade of the programmed death 1 (PD-1) receptor, indicating that the differences in PD-L1 expression between CD44+ and CD44- cells are biologically and clinically relevant.Our findings provide a mechanism by which long-lived CD44+ tumor-initiating cells can selectively evade host immune responses and provide rationale for targeting the PD-1 pathway in the adjuvant therapy setting of SCCHN. A., Farnham, P. J., Segal, E., Chang, H. Y. Decoding global gene expression programs in liver cancer by noninvasive imaging. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here we present a novel biochemical approach, in vivo click selective 2'-hydroxyl acylation and profiling experiment (icSHAPE), which enables the first global view, to our knowledge, of RNA secondary structures in living cells for all four bases. Yang, X. L., KHOSRAVIFAR, R., Chang, H. Y., Baltimore, D. ASYMMETRIC RETRACTION OF GROWTH CONE FILOPODIA FOLLOWING FOCAL INACTIVATION OF CALCINEURIN. Although initially discovered as mRNA-like transcripts that do not encode proteins, recent studies have revealed features of lncRNAs that further distinguish them from mRNAs. Although these studies consistently implicate specific pathways in aging processes, there is little conservation between the individual genes that change. The MALAT-1 noncoding RNA Regulates Cell Mobility by Modulating Gene Expressions, Heterogeneity of Response to Chemotherapy and Recurrence-free Survival in Neoadjuvant Breast Cancer: Results from the I-SPY 1 TRIAL, Identification of genes differentially expressed between control and EHF siRNA transfected HCT116 cells, Fungal allergen extracts-induced gene expression in airway epithelial cells (NCI-H292), Systematic Bias in Genomic Classification Due to Contaminating Normal Tissue in Breast Tumor Samples, Inflammatory activation of airway epithelial cells by pyocyanin. Further, lincRNA-EPS mediates these effects by interacting with heterogeneous nuclear ribonucleoprotein L via a CANACA motif located inits 3' end. Here, we describe purification of mouse DE using fluorescence-activated cell sorting (FACS) and mice harboring a transgene encoding enhanced green fluorescent protein (eGFP) inserted into the Sox17 locus, which is expressed in the embryonic endoderm. Thus, UTX defines an evolutionarily conserved mechanism to enable coordinate transcription of a RB network in cell fate control. These findings clarify the lineage origins of human histiocytic disorders and distinguish dendritic cell disorders from all other myeloid neoplasms. The vascular system is locally specialized to accommodate widely varying blood flow and pressure and the distinct needs of individual tissues. [provided by RefSeq, Feb 2009]. Wu, A. R., Kawahara, T. L., Rapicavoli, N. A., van Riggelen, J., Shroff, E. H., Xu, L., Felsher, D. W., Chang, H. Y., Quake, S. R. Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers. Ransom, R. C., Carter, A. C., Salhotra, A., Leavitt, T., Marecic, O., Murphy, M. P., Lopez, M. L., Wei, Y., Marshall, C. D., Shen, E. Z., Jones, R. E., Sharir, A., Klein, O. D., Chan, C. K., Wan, D. C., Chang, H. Y., Longaker, M. T. Enhancer connectome nominates target genes of inherited risk variants from inflammatory skin disorders. View details for DOI 10.1016/j.cell.2018.07.029, View details for Web of Science ID 000445120000013, View details for DOI 10.1038/s41379-018-0052-4, View details for Web of Science ID 000444569400013. This Review focuses on the emerging biology of rejuvenation through the lens of epigenetic reprogramming. p38 mapmapk Noradrenergic neuronal development is impaired by mutation of the proneural HASH-1 gene in congenital central hypoventilation syndrome (Ondine's curse). We show that immunologic gene sets are the most significantly altered in skin youthfulness (with the most significant gene set p = 2.4x10-5), suggesting the immune system plays an important role in skin youthfulness, a finding that has not previously been recognized. The Sir2 deacetylase regulates chromatin silencing and lifespan in Saccharomyces cerevisiae. Because ZNF217 is amplified in numerous cancers, these results have implications for other cancers.This study finds that ZNF217 is a poor prognostic indicator and therapeutic target in patients with breast cancer and may be a strong biomarker of triciribine treatment efficacy in patients. This analysis included two mice whose genotypes were incorrectly assigned. To date, scaffolds have been shown to be composed of proteinaceous units; however, recent evidence has supported the idea that non-coding RNAs may also play a similar role. Here, we measured structures of an RNA duplex containing m(6)A in the GGACU consensus, along with an unmodified RNA control, by 2D NMR. Structural imprints in vivo decode RNA regulatory mechanisms, Detecting riboSNitches with RNA folding algorithms: a genome-wide benchmark. Arsenite-induced stress shifts DDX3 binding from the 5'UTR into the coding region of mRNAs concomitant with a general reduction of translation, and both the shift of DDX3 on mRNA and decreased translation are blunted by expression of a catalytically-impaired, medulloblastoma-associated DDX3R534H variant. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. The transcription factor PBX3 promotes tumor cell growth through transcriptional suppression of the tumor suppressor p53. Previous studies have shown that SETDB1 can trimethylate H3 on lysine 9, using in vitro or artificial tethering assays. In this study, based on gene expression profiles of fibroblasts from ten anatomic sites, we identify a stereotyped gene expression program in response to serum exposure that appears to reflect the multifaceted role of fibroblasts in wound healing. Here we characterize the transcriptional landscape of the four human HOX loci at five base pair resolution in 11 anatomic sites and identify 231 HOX ncRNAs that extend known transcribed regions by more than 30 kilobases. Small RNA-seq and gene expression analysis reveal a miRNA profile of cancer-susceptibility in ATM deficient human mammary epithelial cells, Expression correlates of the full-length androgen receptor and its splicing variants, Gene expression profile in HHUA treated with telmisartan, Expression profiling shows differential functions and provides potential new diagnostic biomarkers for colorectal serrated adenocarcinoma, Comparison of host cell gene expression in cowpox, monkeypox or vaccinia virus infected cells reveals virus-specific regulation of immune response genes, Rotating wall vessel (RWV) grown A549s compared to monolayer grown A549s, Examination of the role of peptidylarginine deiminase 2 (PAD2) in gene expression in MCF-7 breast cancer cells, Differentiating factors of cumulus cells related to quality of the human oocyte [CadoretPart1], Differentiating factors of cumulus cells related to quality of the human oocyte [CadoretPart3], Differentiating factors of cumulus cells related to quality of the human oocyte [CadoretPart2], Gene expression profile in HHUA treated with scytonemin, EpCAM knock-down in FaDu head and neck carcinoma cells, Differentiating factors of cumulus cells related to quality of the human oocyte, HepG2 treated with Polycyclic Aromatic Hydrocarbons (PAHs), Tumor-derived Tissue Factor Activates Coagulation and Enhances Thrombosis in a Mouse Xenograft Model of Human Pancreatic Cancer, Epidermolysis bullosa associated cutaneous SCC fibroblast expression profiling, Differential metabolic effects of insulin detemir versus NPH in patients with type 2 diabetes, Gene expression of the pigmented and non-pigmented epithelia of the ciliary body of human healthy eyes. Our data suggest that BMP antagonists may be important constituents of tumor stroma, providing a favorable microenvironment for cancer cell survival and expansion in many cancers. Why do long hairs grow on the scalp but not on our palms or soles? One such novel transcript specifically expressed in breast tissue was further evaluated using RNA in situ hybridization on a panel of breast tumors. The Satb1 homeodomain is dispensable for high affinity binding but is essential for specificity. For more information, please contact Joanne Otani, (650) 721 - 2372. We propose that such a secondary network of self-antigen-expressing stromal cells may help reinforce immune tolerance by preventing the maturation of autoreactive T cells that escape thymic negative selection. ChIRP-MS analysis of four ncRNAs captures key protein interactors, including a U1-specific link to the 3' RNA processing machinery. Stem cell regulation and hierarchical organization ofhuman skeletal progenitors remain largely unexplored. Histone H3K27 trimethylation (H3K27me3) has been linked to polycomb-group-protein-mediated suppression of Hox genes and animal body patterning, X-chromosome inactivation and possibly maintenance of embryonic stem cell (ESC) identity. Our findings have captured cellular ontogenies at the chromatin level, identified lineage-specific regulators potentially acting on these sites, and uncovered hallmarks of regulatory plasticity between cell types that suggest mechanisms to regenerate beta cells from pancreatic endocrine or exocrine cells. Chromosome conformation is an important feature of metazoan gene regulation; however, enhancer-promoter contact remodeling during cellular differentiation remains poorly understood. (62)EEEE(65) plays a stabilizing role in the formation of a ternary complex between Nef, the MHC-I cytoplasmic domain, and AP-1; Thrombin Stimulation of c-jun mRNA expression showed biphasic responses with two peaks after 1 and 8 hours of exposure. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Studies in mice suggest that this protein may interact with serum response factor (SRF) and modulate SRF-dependent cardiac-specific gene expression and cardiac development. In addition to membrane delimited organelles, proteins and RNAs can organize themselves into specific domains. ID2 (Inhibitor Of DNA Binding 2) is a Protein Coding gene. View details for DOI 10.1371/journal.pone.0165913, View details for Web of Science ID 000387724300066, View details for PubMedCentralID PMC5102383. Gender was the most significant attributable source of variation. Finally, we combine gene expression and epigenetic data of mouse skeletal stem cells (mSSCs) and hSSCs to identify evolutionarily conserved and divergent pathways driving SSC-mediated skeletogenesis. Expression of the TGFbeta-responsive signature was examined in skin biopsies from 17 dSSc, seven limited SSc (lSSc), three morphea patients, and six healthy controls. We review the evidence linking lncRNAs to diverse human diseases and highlight fundamental concepts in lncRNA biology that still need to be clarified to provide a robust framework for lncRNA genetics. The cytotopic structuromes substantially expand RNA structural information and enable detailed investigation of the central role of RNA structure in linking transcription, translation and RNA decay. The TGFbeta-responsive signature was expressed in 10 out of 17 dSSc skin biopsies, but was not found in lSSc, morphea, or healthy control biopsies. HOTAIR interacts with Polycomb Repressive Complex 2 (PRC2) and is required for PRC2 occupancy and histone H3 lysine-27 trimethylation of HOXD locus. Chang, H. Y., Chi, J. T., Dudoit, S., Bondre, C., van de Rijn, M., Botstein, D., Brown, P. O. Proteases for cell suicide: Functions and regulation of caspases, Dissecting Fas signaling with an altered-specificity death-domain mutant: Requirement of FADD binding for apoptosis but not Jun N-terminal kinase activation, Activation of apoptosis signal regulating kinase 1 (ASK1) by the adapter protein Daxx. Long intergenic noncoding RNAs (lincRNAs) regulate chromatin states and epigenetic inheritance. Oxidative damage and respiratory burst in Multiple Sclerosis, Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma, Meta-analysis of Clear Cell Renal Cell Carcinoma Gene Expression Defines a Variant Subgroup and Identifies Gender Influences on Tumor Biology, ICL002: Time course of Calu-3 cells infected with Influenza A/VN/1203/04, Protein coding gene expression profile of dasatinib-treated chronic myeloid leukemia patients with resistance to imatinib, TCL001: Calu-3 cells treated with either IFN alpha or gamma, SCL005: icSARS CoV Urbani or icSARS deltaORF6 infections of the 2B4 clonal derivative of Calu-3 cells - Time course, Expression of motor proteins in transgenic HeLa cell lines, Transcriptome analysis of primary human CD4+ T-cell activation, Transcriptome analysis of primary human monocyte differentiation, Castration-Resistant Prostate Cancer (CRPC), Gene expression signatures of dasatinib-treated chronic myeloid leukemia patients with resistance to imatinib, Normal breast tissue of obese women is enriched for macrophage markers and macrophage-associated gene expression, Whole genome gene expression profiling in Adult T-cell Leukemia (ATL) cells and in Normal CD4+ T-cells, Epstein-Barr Virus (EBV)-positive B-cell strain, 28-2: Low v. High latent membrane protein 1 (LMP1)-mRFP expression. Carter, A. C., Chang, H. Y., Church, G., Dombkowski, A., Ecker, J. R., Gil, E., Giresi, P. G., Greely, H., Greenleaf, W. J., Hacohen, N., He, C., Hill, D., Ko, J., Kohane, I., Kundaje, A., Palmer, M., Snyder, M. P., Tung, J., Urban, A., Vidal, M., Wong, W. Mechanistic insights in X-chromosome inactivation. A patient with myelodysplastic syndrome presented with an acute eruption of bilateral, lower-extremity, tender, indurated, brown plaques that clinically resembled chronic stasis dermatitis. These results highlight the potentially broad contribution of RNA structure and its variation to gene regulation. Ensembl, locations according to GeneLoc Chi, J. T., Chang, H. Y., Haraldsen, G., Jahnsen, F. L., Troyanskaya, O. G., Chang, D. S., Wang, Z., Rockson, S. G., van de Rijn, M., Botstein, D., Brown, P. O. Eruptive xanthomas associated with olanzapine use. Simultaneous measurement of cell lineage and cell fates is a longstanding goal in biomedicine. View details for DOI 10.1038/jid.2009.318, View details for Web of Science ID 000275017600013. TNF regulates hundreds of lncRNAs, including 54 pseudogene lncRNAs, several of which show exquisitely selective expression in response to specific cytokines and microbial components in a NF-B-dependent manner. We apply PARS to profile the secondary structure of the messenger RNAs (mRNAs) of the budding yeast Saccharomyces cerevisiae and obtain structural profiles for over 3,000 distinct transcripts. - Achaete-Scute Family BHLH Transcription Factor 1, Achaete-Scute Family BHLH Transcription Factor 1, Class A Basic Helix-Loop-Helix Protein 46, Achaete-Scute Complex (Drosophila) Homolog-Like 1, Achaete-Scute Complex Homolog 1 (Drosophila), Achaete-Scute Complex-Like 1 (Drosophila), Tocris Summary , Finally, we identified Zfp238 as a key Ascl1 target gene that can partially substitute for Ascl1 during iN cell reprogramming. Here we discover and characterize the sets of mouse lncRNAs induced by inflammatory signaling via TNF. View details for Web of Science ID 000078698400018. Simeonov, D. R., Gowen, B. G., Boontanrart, M. n., Roth, T. L., Gagnon, J. D., Mumbach, M. R., Satpathy, A. T., Lee, Y. n., Bray, N. L., Chan, A. Y., Lituiev, D. S., Nguyen, M. L., Gate, R. E., Subramaniam, M. n., Li, Z. n., Woo, J. M., Mitros, T. n., Ray, G. J., Curie, G. L., Naddaf, N. n., Chu, J. S., Ma, H. n., Boyer, E. n., Van Gool, F. n., Huang, H. n., Liu, R. n., Tobin, V. R., Schumann, K. n., Daly, M. J., Farh, K. K., Ansel, K. M., Ye, C. J., Greenleaf, W. J., Anderson, M. S., Bluestone, J. By further characterizing RAPs, we discover the presence of ufmylation, a metazoan-specific post-translational modification (PTM), on ribosomes and define its direct substrates. For more information, please contact Joanne Otani, (650) 721 - 2372. Profiling of RWPE cells stably over-expressing ETV1: GSE7702: Comparison of the prostate cancer cell line LNCaP and its androgen insensitive derivative C4-2B: GSE7900: Gene expression in undifferentiated human ES cells - Agilent The gene expression programs of human fibroblasts largely reflect the superimposition of three gene expression profiles that demarcate the fibroblast's position relative to three developmental axes. While some lncRNAs are thought to work in cis on neighboring genes, other lncRNAs work in trans to regulate distantly located genes. Single-cell ATAC-seq (scATAC-seq) maps from hundreds of single cells in aggregate closely resemble accessibility profiles from tens of millions of cells and provide insights into cell-to-cell variation. The occupancy sites of most lncRNAs are not known, and the roles of lncRNAs in chromatin regulation have been mostly inferred from the indirect effects of lncRNA perturbation. Pan-cancer analyses reveal that oncogenes encoded on ecDNA are among the most highly expressed genes in the transcriptome of the tumours, linking increased copy number with high transcription levels. 2012), Peripheral neuron-like cells(Lee G et. A second replication group (n=371) confirmed rs318125, downstream of DIAPH2 (diaphanous homolog 2 (Drosophila)) (Pallele=0.010, Pgenotype=0.002) and rs7616661, downstream of EDEM1 (ER degradation enhancer, mannosidase -like 1) (Pgenotype=0.042). Similarly to miRNAs, lincRNAs exhibit distinct gene expression patterns in primary tumors and metastases. 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