Arda, H. E., Li, L., Tsai, J., Torre, E. A., Rosli, Y., Peiris, H., Spitale, R. C., Dai, C., Gu, X., Qu, K., Wang, P., Wang, J., Grompe, M., Scharfmann, R., Snyder, M. S., Bottino, R., Powers, A. C., Chang, H. Y., Kim, S. K. Medulloblastoma-associated DDX3 variant selectively alters the translational response to stress. A. TFAP2C-and p63-Dependent Networks Sequentially Rearrange Chromatin Landscapes to Drive Human Epidermal Lineage Commitment. View details for DOI 10.1016/j.molcel.2012.08.008. Transcription Factor Targeted Genes and Li, L., Liu, B., Wapinski, O. L., Tsai, M., Qu, K., Zhang, J., Carlson, J. C., Lin, M., Fang, F., Gupta, R. A., Helms, J. A thorough understanding of how stem cells in the skeleton interpret mechanical stimuli and enact regeneration would shed light on how forces are transduced to the nucleus in regenerative processes. When different types of functional genomics data are generated on single cells from different samples of cells from the same heterogeneous population, the clustering of cells in the different samples should be coupled. Here, we present HiChIRP, a method leveraging bio-orthogonal chemistry and optimized chromosome conformation capture conditions, which enables interrogation of chromatin architecture focused around a specific RNA of interest down to approximately ten copies per cell. CRISPR Clones for HOPX - Starting at $85 >, VectorBuilder CRISPR vectors for HOPX (ie. Hox genes encode transcription factors that specify embryonic positional identity in cells and guide tissue differentiation. Optimal modulation of both CAF-1 and transcription factor levels increased reprogramming efficiency by several orders of magnitude and facilitated iPS cell formation in as little as 4 days. Our results indicate that the downregulation of cyclin D2 expression by PTEN is mediated by the GSK3beta/beta-catenin/TCF pathway in cooperation with CREB, and suggest a convergence from the PI-3 kinase/PTEN pathway and the Wnt pathway in modulation of cyclin D2 expression. Conversely, loss of HOTAIR can inhibit cancer invasiveness, particularly in cells that possess excessive PRC2 activity. Kawahara, T. L., Michishita, E., Adler, A. S., Damian, M., Berber, E., Lin, M., McCord, R. A., Ongaigui, K. C., Boxer, L. D., Chang, H. Y., Chua, K. F. Global Expression Profiling in Atopic Eczema Reveals Reciprocal Expression of Inflammatory and Lipid Genes. 8600 Rockville Pike N6-methyl-adenosine (m(6)A) is the most abundant modification on messenger RNAs and is linked to human diseases, but its functions in mammalian development are poorly understood. View details for DOI 10.1016/j.molcel.2016.03.013. These different cell types must be correctly arranged in spatial patterns to make functioning tissues and organs. 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 Together, these findings identify lincRNA-EPS as a repressor of inflammatory responses, highlighting the importance of lincRNAs in the immune system. These three groups are (1) quiescent WS/non-hypoxic HS; (2) activated WS/non-hypoxic HS or quiescent WS/hypoxic tumours and (3) activated WS/hypoxic HS. View details for DOI 10.1038/s41467-018-07115-y, View details for Web of Science ID 000449069600012. Widely expressed. These domains constitute the minimal RNA unit present in multiple copies in diverse arrangements for nucleation of the MSL complex. In the constellation of genes differentially expressed in AE skin compared to healthy control skin, we have identified several potential susceptibility genes that may play a critical role in the pathological condition of AE. Hence the information content in RNA is not simply its linear sequence of bases, but is also encoded in complex folding of RNA molecules. The sentence "This enhancer deletion (EDEL) strain also had no obvious T cell phenotypes at steady state (Extended Data Fig. HiChIRP reveals RNA-associated chromosome conformation. Segal, E., Sirlin, C. B., Ooi, C., Adler, A. S., Gollub, J., Chen, X., Chan, B. K., Matcuk, G. R., Barry, C. T., Chang, H. Y., Kuo, M. D. A transcriptional program mediating entry into cellular quiescence. We anticipate that scATAC-seq will enable the unbiased discovery of gene regulatory factors across diverse biological systems. View details for DOI 10.1016/j.molcel.2011.08.018. View details for DOI 10.1016/j.cell.2019.05.027. Although overall aggregate algorithmic performance on the full set of riboSNitches is relatively low, significant improvement is possible if the highest confidence predictions are evaluated independently. Self-renewal is a hallmark of stem cells and cancer, but existence of a shared stemness program remains controversial. ATAC-seq revealed previously undescribed elements that escape X chromosome inactivation and predicted gender-specific gene regulatory networks across autosomes, which coordinately affect genes with immune function. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. These results indicate that epigenetic derepression by JMJD3 controls mammalian epidermal differentiation. Recent progress suggests that the involvement of lncRNAs in human diseases could be far more prevalent than previously appreciated. View details for DOI 10.1016/j.stem.2015.09.017, View details for Web of Science ID 000366139100010. Ensembl, locations according to GeneLoc Epigenomics Technologies and Applications, Rapid chromatin repression by Aire provides precise control of immune tolerance. Here, we construct a gene module map to systematically relate transcriptional programs in embryonic stem cells (ESCs), adult tissue stem cells, and human cancers. In epidermis, ANCR loss abolished the normal exclusion of differentiation from the progenitor-containing compartment. The fact that HOTAIR drives chromatin reprogramming genome-wide suggests that long-range regulation by lncRNAs may be a widespread mechanism. GENATLAS. This analysis included two mice whose genotypes were incorrectly assigned. In addition to membrane delimited organelles, proteins and RNAs can organize themselves into specific domains. 2011), Bone marrow-derived mesenchymal stem cells, Applied Biosystems by Thermo Fisher Scientific TaqMan Assays for ASCL1, SNP Genotyping and Copy Number Assays for research, See all genomic literature for ASCL1 gene in Mastermind, ATLAS of Genetics and Cytogenetics in Oncology and Haematology, Search disorders for ASCL1 gene in PubMed and other databases, Search for latest publications for ASCL1 gene in PubMed and other databases, 2 R&D Systems ASCL1 (ASCL1/Mash1) Products, 2 R&D Systems ASCL1 (ASCL1/Mash1) Primary Antibodies, R&D Systems custom ASCL1 antibody, protein, and immunoassay development services, High-throughput Antibody Production Service, Epitope Tag Antibodies & Reporter Protein Antibodies, Search Knockout (KO) Validated Antibodies, Find your next knockout model in the Taconic Knockout Repository, Genetically Engineered Models Available Immediately, View All CRISPR Kits, Synthetic sgRNA, and Screening Library Products, View All Engineered Cells Products, Including Edited iPSCs, Contact Sales to Request a Quote or More Information, Abnormality of the musculoskeletal system. Some genomic regions harbor multiple, regularly spaced Satb1 binding motifs (typical separation ~1 turn of the DNA helix) characterized by highly cooperative binding. 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. Stomach - Gastrointestinal stromal tumor (GIST) Activating mutations in the proto-oncogene KIT (~75%) (Science 1998;279:577) or platelet derived growth factor receptor- (PDGFR-) (~10%) (Science 2003;299:708) . Mechanistic insights in X-chromosome inactivation, The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline. The vascular system is locally specialized to accommodate widely varying blood flow and pressure and the distinct needs of individual tissues. The ANCR lncRNA is thus required to enforce the undifferentiated cell state within epidermis. 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. Here we introduce a UV-C crosslinking and immunoprecipitation platform, irCLIP, which provides an ultraefficient, fast, and nonisotopic method for the detection of protein-RNA interactions using far less material than standard protocols. 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. SWANSON, S. K., Born, T., ZYDOWSKY, L. D., Cho, H. J., Chang, H. Y., Walsh, C. T., Rusnak, F. Freeman Spogli Institute for International Studies, Institute for Computational and Mathematical Engineering (ICME), Institute for Human-Centered Artificial Intelligence (HAI), Institute for Stem Cell Biology and Regenerative Medicine, Stanford Institute for Economic Policy Research (SIEPR), Stanford Woods Institute for the Environment, Office of VP for University Human Resources, Office of Vice President for Business Affairs and Chief Financial Officer, Maternal & Child Health Research Institute (MCHRI), Directed Reading in Stem Cell Biology and Regenerative Medicine, DOI 10.1146/annurev-biochem-051410-092902, DOI 10.1146/annurev.biochem.78.071107.134639. Large intervening non-coding RNAs (lincRNAs) are pervasively transcribed in the genome yet their potential involvement in human disease is not well understood. We collected single-cell chromatin accessibility profiles across 10 populations of immunophenotypically defined human hematopoietic cell types and constructed a chromatin accessibility landscape of human hematopoiesis to characterize differentiation trajectories. 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. Genetic blockade of NFkappaB in the skin of chronologically aged mice reversed the global gene expression program and tissue characteristics to those of young mice, demonstrating for the first time that disruption of a single gene is sufficient to reverse features of aging, at least for the short-term. Technologies to probe functions and mechanisms of long noncoding RNAs. Gene expression profiles of MCF7 with CARM1 knocked down, Gene expression profiles of different subpopulations of hepatocellular carcinoma, Respiratory chain protein analysis and gene expression profiles of fibroblast cell lines from 9 patients with SURF1 gene mutations, Interactions with Fibroblasts are Distinct in Basal-like and Luminal Breast Cancers, Chlamydia trachomatis serogroup D disturbs epithelial tissue homeostasis in Fallopian tubes via paracrine Wnt signalling, MYBPH, a novel transcriptional target of NKX2-1/TTF-1, inhibits ROCK1 and actomyosin assembly, and reduces cell motility and tumor metastasis, Gene expression-based, individualized diagnostic GC/ABC prediction for relapse/refractory diffuse large B cell lymphoma (DLBCL), Gene expression profile of H1 human embryonic stem cells, IMR90 lung fibroblasts, calcium induced keratinocytes, and primary hepatocytes, Gene expression profile of H1.5 knockdown and SIRT1 knockdown IMR90 cells versus control cells, Gene Regulation by the Human Glucocorticoid Receptor Dimerization Domain Mutant dim4, Comparable mRNA expression of pluripotency-related genes in SNUhES3 cells cultured on autofeeder or xenofeeder system, Coordinated regulation of polycomb group complexes through microRNAs in cancer, GATA6 Activates Wnt Signaling in Pancreatic Cancer by Negatively Regulating the Wnt Antagonist Dickkopf-1, Comparative gene expression profiles induced by PPAR and PPAR/ agonists in human hepatocytes, Role of Aldoketoreductases and Other Doxorubicin Pharmacokinetic Genes in Doxorubicin Resistance, DNA binding, and Subcellular Localization, Genomic differences distinguish the myofibroblast phenotype of distal lung from airway fibroblasts, Microarray Analysis of Genes Regulated by Macrophage-Conditioned Media Treatment of Human Pre-Adipocytes, Agilent expression analysis of prostate cancer tissue samples, Deep sequencing reveals distinct patterns of DNA methylation and transcript isoform regulation in prostate cancer, Suppression of breast tumor growth and metastasis by an engineered transcription factor, Gene expression analysis of mesenchymal stem cells (MSC), osteoblasts and the U2OS (osteosarcoma) cell line, Transcription profiling of human olfactory ecto-mesenchymal stem cells (hOE-MSCs) from familial dysautonomia (FD) patients with or without kinetin treatment, Differential Gene Expression between African American and European American Colorectal Cancer Patients, Impact of Visceral Fat on Gene Expression Profile in Peripheral Blood Cells, Identification of novel target genes of nerve growth factor (NGF) in human mastocytoma cell line (HMC-1 (V560G c-Kit)) by transcriptome analysis, COMPARISON OF DORSOCERVICAL TO ABDOMINAL SUBCUTANEOUS ADIPOSE TISSUE IN PATIENTS WITH AND WITHOUT ANTIRETROVIRAL THERAPY-ASSOCIATED LIPODYSTROPHY, Comparison of gene expression profiles of A549 cell treated with NRF2 siRNA and control siRNA, Peripheral blood lymphocytes: ALS patients vs. healthy controls, Microarray-based identification of age-dependent differences in gene expression of human dermal fibroblasts, miR-142-3p over-expression in the Raji B-cell line, Hey3Met2 human ovarian cancer cells overexpressing wild type or catalytically-dead mutant RNASET2, The tumor suppressor gene rap1GAP is silenced by mir-101-mediated EZH2 overexpression in invasive squamous cell carcinoma, cDNA microarray analysis of miR-1 transfected HeLa and NPC-TW01 cells, Comparisson between tumour and healthy prostate glands, Pathway and functional association analysis of whole blood gene expression profiles reveal functional networks underlying TB pathogenesis. To achieve high selectivity within the crowded cellular milieu the cell utilizes scaffolding complexes whose role is to bring molecules in proximity thereby controlling and enhancing intermolecular interactions and signaling events. B., Hastie, T., Tibshirani, R., Sorlie, T., Dai, H. Y., He, Y. D., Van't Veer, L. J., Bartelink, H., van de Rijn, M., Brown, P. O., van de Vijver, M. J. Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds. We identify a dominant role for hypoxia, marked by HIF1alpha protein, in the tumor microvenvironment for shaping the regulome in a subset of epithelial tumor cells. 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 View details for DOI 10.1016/j.cell.2013.09.028. View details for DOI 10.1016/j.molcel.2008.12.016. We have previously demonstrated that the expression level of lncRNA in the HOX locus, including HOTAIR, is a predictor of breast cancer metastasis. Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lncRNAs with bound protein and DNA sequences, which are enumerated by deep sequencing. View details for Web of Science ID A1992HR85300015, Director, NIH Center of Excellence in Genomic Science: Little is known about the functional domain architecture of long noncoding RNAs (lncRNAs) because of a relative paucity of suitable methods to analyze RNA function at a domain level. Sustained angiogenesis, through either local sprouting (angiogenesis) or the recruitment of bone marrow-derived cells (BMDCs) (vasculogenesis), is essential to the development of a tumor. Expression of SIX2 and SIX3, transcription factors without prior known functions in the pancreas and linked to fasting hyperglycemia risk, increased with age specifically in human islet cells. By probing yeast RNA structures at different temperatures, we obtained relative melting temperatures (Tm) for RNA structures in over 4000 transcripts. Depleting ANCR in progenitor-containing populations, without any other stimuli, led to rapid differentiation gene induction. The exosome complex recognizes unpaired bases during heat shock to degrade these RNAs, coupling intrinsic structural stabilities to gene regulation. We have previously shown that the Polycomb repressive complex 2 is responsible for mediating trimethylation of lysine 27 of histone H3 in human cancer cells. While much is known about genes that promote aging, little is known about genes that protect against or prevent aging, particularly in human skin. Although the vast majority of lncRNAs have no known function, recurring molecular mechanisms for lncRNAs are now being observed in chromatin regulation and cancer pathways and emerging technologies are now providing tools to interrogate lncRNA molecular interactions and determine function of these abundant cellular macromolecules. Systematic reconstruction of RNA functional motifs with high-throughput microfluidics. SNP-containing enhancers from inflammatory skin conditions were significantly enriched within the human leukocyte antigen (HLA)-locus, and also targeted several key factors from the JAK-STAT signaling pathway, while non-immune conditions did not. Potential roles of lincRNAs in gene activation are much less understood. Arda, H., Tsai, J., Rosli, Y. R., Giresi, P., Bottino, R., Greenleaf, W. J., Chang, H. Y., Kim, S. K. Identification of the Human Skeletal Stem Cell. Importantly, morpholino oligonucleotide inhibition of a zebrafish UTX homologue resulted in mis-regulation of hox genes and a striking posterior developmental defect, which was partially rescued by wild-type, but not by catalytically inactive, human UTX. An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma. Based on kinetic data, substrate specificity, and procaspase structure, caspases have been conceptually divided into initiators and effectors. The Satb1 genome organizer regulates multiple cellular and developmental processes. The discovery of extensive transcription of large RNA transcripts that do not code for proteins, termed long noncoding RNAs (lncRNAs), provides an important new perspective on the centrality of RNA in gene regulation. Revealing long noncoding RNA architecture and functions using domain-specific chromatin isolation by RNA purification. Human tumors consist of heterogeneous populations of cells with distinct marker expression and functional properties. Long noncoding RNAs are key regulators of chromatin states for important biological processes such as dosage compensation, imprinting, and developmental gene expression (1,2,3,4,5,6,7). A fundamental feature of the architecture and functional design of vertebrate animals is a stroma, composed of extracellular matrix and mesenchymal cells, which provides a structural scaffold and conduit for blood and lymphatic vessels, nerves, and leukocytes. View details for DOI 10.1158/2159-8290.CD-12-0093, View details for Web of Science ID 000306365800042, View details for PubMedCentralID PMC3546490. RNA structure is important for RNA function and regulation, and there is growing interest in determining the RNA structure of many transcripts. Sinha, S., Adler, A. S., Field, Y., Chang, H. Y., Segal, E. A dermal HOX transcriptional program regulates site-specific epidermal fate. Purified RNA is then reverse-transcribed to produce cDNA, with SHAPE-modified bases leading to truncated cDNA. Deficiency of mammalian SIRT6 leads to shortened life span and an aging-like phenotype in mice, but the underlying molecular mechanisms are unclear. ZBTB46 is a zinc finger and BTB domain-containing transcription factor, which is expressed by dendritic cells and committed dendritic cell precursors, but not by plasmacytoid dendritic cells, monocytes, macrophages, or other immune cell populations. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. Eukaryotic genomes are packaged into chromatin, where diverse histone modifications can demarcate chromatin domains that facilitate or block gene expression. NEUROD1 (Neuronal Differentiation 1) is a Protein Coding gene. To investigate such protein interactions, we establish a ribosome affinity purification method that unexpectedly identifies hundreds of ribosome-associated proteins (RAPs) from categories including metabolism and cell cycle, as well as RNA- and protein-modifying enzymes that functionally diversify mammalian ribosomes. Currently the complexity of the protocol and the amount of hands-on time required for this assay limits its use to low throughput applications; furthermore, variability in antibody quality poses an additional obstacle in scaling up ChIP for large scale screening purposes. A., Sdhof, T. C., Wernig, M. Transcription coactivator and lncRNA duet evoke Hox genes, Gpr124 is essential for blood-brain barrier integrity in central nervous system disease. This raises the fundamental question of whether lineage reprogramming is possible between cell types derived fromdifferent germ layers. 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. Skin youthfulness was defined as the top 10% of individuals whose assessed skin aging features were most discrepant with their chronological ages. Calo, E., Flynn, R. A., Martin, L., Spitale, R. C., Chang, H. Y., Wysocka, J. The ESC-like transcriptional program is activated in diverse human epithelial cancers and strongly predicts metastasis and death. Microarrays have been applied in stem cell research to identify major features or expression signatures that define stem cells and characterize their differentiation programs toward specific lineages. The generation of defined populations of functionally mature human GABAergic neurons represents an important step toward enabling the study of diseases affecting inhibitory synaptic transmission. Elevated levels of either wild-type ETV1 or its truncated derivative, dETV1, which mimics the product of an oncogenic rearrangement in certain tumors, results in increased expression of mRNA for p14ARF, a known activator of p53. Consistent with these findings, inhibitors of CDK7 reverse HOXC10-mediated drug resistance in cultured cells. Alastalo, T., Li, M., Perez, V. D., Pham, D., Sawada, H., Wang, J. K., Koskenvuo, M., Wang, L., Freeman, B. Here we demonstrate that lncRNAs guide the organismal DNA damage response. As new lncRNAs are being discovered at a rapid pace, the molecular mechanisms of lncRNAs are likely to be enriched and diversified. This gene was present in the common ancestor of animals. Initiation of apopotosis requires the conversion of procaspases to mature caspases. Long noncoding RNAs (lncRNAs) regulate diverse processes, yet a potential role for lncRNAs in maintaining the undifferentiated state in somatic tissue progenitor cells remains uncharacterized. CRISPR Clones for ASCL1 - Starting at $85 >, Browse OriGene Inhibitory RNA Products For ASCL1, Validated shRNA from LipExoGen - Guaranteed knockdown for any gene - 10 days or less, Custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling, LipExoGen Custom Lentivirus Services - Fast Turnaround - shRNA, sgRNA, miRNA, cDNA, and reporters (TFs, signal pathway, gene promoter), ASCL1 CRISPR Engineered iPSC Disease Model, Contact an Expert about Cell Line Engineering, "Oligodendrocyte specification and differentiation, leading to myelin components for CNS", Neurogenesis regulation in the olfactory epithelium, Embryonic and Induced Pluripotent Stem Cells and Lineage-specific Markers, Neural Stem Cells and Lineage-specific Markers, Lateral Ganglionic Eminence Progenitor Cells, Caudal Ganglionic Eminence Progenitor Cells, Medial Ganglionic Eminence Progenitor Cells, N2/LSB/S/F8-induced cells(Kriks S et. These results identify a conserved network of regulatory pathways underlying mammalian aging and show that NF-kappaB is continually required to enforce many features of aging in a tissue-specific manner. 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. Thus, numerous lncRNAs may be modulated as a class in development and disease, notably where Dcr and cMyc act. Chang, H. Y., Takei, K., SYDOR, A. M., Born, T., Rusnak, F., Jay, D. G. ACTIVATION OF CLN1 AND CLN2 G(1) CYCLIN GENE-EXPRESSION BY BCK2, ACTIVE-SITE MUTANTS OF HUMAN CYCLOPHILIN-A SEPARATE PEPTIDYL-PROLYL ISOMERASE ACTIVITY FROM CYCLOSPORINE-A BINDING AND CALCINEURIN INHIBITION. Diseases associated with NEUROD1 include Maturity-Onset Diabetes Of The Young, Type 6 and Type 2 Diabetes Mellitus.Among its related pathways are Regulation of beta-cell development and Nervous system development.Gene Ontology (GO) annotations related to this gene include Here, we reveal a layer of transcriptome organization in the form of RNA folding energies. Congenital Central Hypoventilation Syndrome; Central Hypoventilation Syndrome, Congenital, 1, Conflicting Interpretations: A quantitative metric of mRNA-lncRNA decoupling revealed that Dcr and cMyc differentially regulate lncRNAs versus mRNAs in diverse cell types and in vivo. NeST RNA was found to bind WDR5, a component of the histone H3 lysine 4 methyltransferase complex, and to alter histone 3 methylation at the IFN- locus. View details for Web of Science ID A1992JR69300003. The founding member of this family was identified as a gene In tranfected tissue culture cells, FasDelta activated Jun N-terminal kinase normally but was impaired in cell death induction. 1), lead to relocalization of DDX21 from the nucleolus to the nucleoplasm, its loss from the chromatin targets, as well as inhibition of rRNA processing and downregulation of ribosomal protein gene transcription. Here we develop a systematic approach to identify combinatorial cis-regulatory motifs that drive age-dependent gene expression across different tissues and organisms. It was shown to correlate with low tumor grade and estrogen receptor expression, thereby representing a potentially important new breast cancer biomarker. View details for DOI 10.1016/j.stem.2014.09.019. Mechanotransduction via FAK in skeletal stem cells during distraction activates a gene-regulatory program and retrotransposons that are normally active in primitive neural crest cells, from which skeletal stem cells arise during development. However, fibroblasts represent heterogeneous mesenchymal progenitor cells that potentially contain neural crest lineages, and the cell of origin remained undefined. Single-cell RNA-seq in samples from the human neocortex demonstrate that long noncoding RNAs (lncRNAs) are abundantly expressed in specific individual brain cells, despite being hard to detect in bulk samples. Here, by integrating ultrastructural imaging, long-range optical mapping and computational analysis of whole-genome sequencing, we demonstrate the structure of circular ecDNA. FTC-238/hrTPO/RSK008 treated with thyroid peroxidase-disrupting chemicals. Structural imprints in vivo decode RNA regulatory mechanisms, Detecting riboSNitches with RNA folding algorithms: a genome-wide benchmark. Approaches to differentiating pluripotent stem cells (PSCs) into neurons currently face two major challenges-(i) generated cells are immature, with limited functional properties; and (ii) cultures exhibit heterogeneous neuronal subtypes and maturation stages. In the epidermis, a tissue that balances stem cell self-renewal with differentiation, H3K27me3, occupies the promoters of many differentiation genes. Mechanistically, TFAP2C primes the surface ectoderm chromatin landscape and induces p63 expression and binding sites, thus allowing maturation factor p63 to positively autoregulate its own expression and close a subset of the TFAP2C-initiated surface ectoderm program. Here we show that transcription is quantitatively different for lncRNAs and mRNAs--as revealed by deficiency of Dicer (Dcr), a key RNase that generates microRNAs (miRNAs). 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. Although many expression signatures show promise in predicting patient prognosis or response to therapies, the usefulness of the signatures in understanding the underlying mechanisms of cancer has not been fully exploited. Tumours were assigned to three prognostic groups using the previously reported Wound-response and hypoxia-response signatures, and the outcome in each of these subgroups was evaluated.We have assigned invasive breast carcinomas from 295 stages I and II breast cancer patients to three groups based on gene expression profiles subdivided by the wound-response signature (WS) and hypoxia-response signature (HS). Restoration of proper organ function often requires restoring homeostatic gene regulation. Microarray analysis of genes impacted by 5 day knockdown of SLC24A5 in normal human melanocytes. Many craniofacial disorders are caused by heterozygous mutations in general regulators of housekeeping cellular functions such as transcription or ribosome biogenesis. View details for DOI 10.1016/j.cell.2007.05.022. Harcourt, E. M., Ehrenschwender, T., Batista, P. J., Chang, H. Y., Kool, E. T. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. In the classic genetic model Caenorhabditis elegans, the pro-apoptotic protein CED-4 activates the CED-3 caspase and is inhibited by the Bcl-2-like protein CED-9. View details for Web of Science ID 000075666800051. Learning more from microarrays: Insights from modules and networks, Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. View details for DOI 10.1016/j.sbi.2016.01.007, View details for Web of Science ID 000372681200019, View details for PubMedCentralID PMC4785074. Tissue-specific expression patterns in different tissue microvascular ECs suggest they are distinct differentiated cell types that play roles in the local physiology of their respective organs and tissues. Xu, J., Spitale, R. C., Guan, L., Flynn, R. A., Torre, E. A., Li, R., Reber, I., Qu, K., Kern, D., Knaggs, H. E., Chang, H. Y., Chang, A. L. HiChIP: efficient and sensitive analysis of protein-directed genome architecture. Zheng, G. X., Do, B. T., Webster, D. E., Khavari, P. A., Chang, H. Y. Dicer-microRNA-Myc circuit promotes transcription of hundreds of long noncoding RNAs. ChIRP is applicable to many lncRNAs because the design of affinity-probes is straightforward given the RNA sequence and requires no knowledge of the RNA's structure or functional domains. However, whether the T cell response to checkpoint blockade relies on reinvigoration of pre-existing tumor-infiltrating lymphocytes or on recruitment of novel T cells remains unclear2-4. Here, we describe a multimodal strategy for isolating pancreatic endocrine and exocrine cells from children and adults to identify age-dependent gene expression and chromatin changes on a genomic scale. However, previous whole-cell analyses lacked the resolution to unravel the landscape and also the regulatory mechanisms of RNA structural changes across subcellular compartments. Notably, suppression of CAF-1 also enhanced the direct conversion of B cells into macrophages and fibroblasts into neurons. not specified, Likely Benign: Embryonic definitive endoderm (DE) generates the epithelial compartment of vital organs such as liver, pancreas, and intestine. Hence, BBL treatment can restore gene expression pattern of photoaged and intrinsically aged human skin to resemble young skin. 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. View details for DOI 10.1182/blood-2012-04-423061. View details for Web of Science ID 000243169100015, View details for PubMedCentralID PMC1779489. Here we report the identification of extrathymic Aire-expressing cells (eTACs) resident within the secondary lymphoid organs. Rinn, J. L., Wang, J. K., Allen, N., Brugmann, S. A., Mikels, A. J., Liu, H., Ridky, T. W., Stadler, H. S., Nusse, R., Helms, J. A set of 337 genes that varied according to these positional divisions was able to group all 47 samples by their anatomic sites of origin. 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. Self-renewing and multipotent hSSCs are present in fetal and adult bones and can also be derived from BMP2-treated human adipose stroma (B-HAS) and induced pluripotent stem cells (iPSCs). By in silico screening, we identified candidate therapeutics that at low concentrations inhibit growth of cancer cells expressing high ZNF217. This is supported by a study showing that > 20% of tested lncRNAs are bound by PRC2 and other chromatin modifiers[10]. This gene encodes a secreted ligand of the glial cell line-derived neurotrophic factor (GDNF) subfamily and TGF-beta (transforming growth factor-beta) superfamily of proteins. Quantitative analysis of RNA-protein interactions on a massively parallel array reveals biophysical and evolutionary landscapes. Together, our findings reveal the histone chaperone CAF-1 to be a novel regulator of somatic cell identity during transcription-factor-induced cell-fate transitions and provide a potential strategy to modulate cellular plasticity in a regenerative setting. Promoter of lncRNA Gene PVT1 Is a Tumor-Suppressor DNA Boundary Element. Transgenic expression of NeST lncRNA alone was sufficient to confer all phenotypes of the SJL/J locus. 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. View details for Web of Science ID A1997XG83000011. This gene is overexpressed in Skin (13.0), Oral epithelium (11.8), Esophagus (6.6), and Heart (6.6). Thus, gene module maps may enable rapid translation of complex genomic signatures in human disease to targeted therapeutic strategies. Siprashvili, Z., Webster, D. E., Kretz, M., Johnston, D., Rinn, J. L., Chang, H. Y., Khavari, P. A. Genome-wide Measurement of RNA Folding Energies. The principal cells of stromal tissue are called fibroblasts, a catch-all designation that belies their diversity. We also validate a novel role for the RNA-binding protein LIN28A as an N6-methyladenosine modification 'anti-reader'. Here we show that dynamic imaging traits in non-invasive computed tomography (CT) systematically correlate with the global gene expression programs of primary human liver cancer. Discovery of stimulation-responsive immune enhancers with CRISPR activation. View details for DOI 10.1016/B978-0-12-803506-1.00002-4, View details for Web of Science ID 000439190900026. Van Gool, F., Nguyen, M. T., Mumbach, M. R., Satpathy, A. T., Rosenthal, W. L., Giacometti, S., Le, D. T., Liu, W., Brusko, T. M., Anderson, M. S., Rudensky, A. Y., Marson, A., Chang, H. Y., Bluestone, J. Expression of the transcription factor ZBTB46 distinguishes human histiocytic disorders of classical dendritic cell origin. Although blood-brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. In the absence of CLN3, bck2 mutations cause an extremely slow growth rate: the cells accumulate in late G1 with very low levels of CLN1 and CLN2 RNA. The proteins W121A (Liu, J., Chen, C.-M., & Walsh, C.T., 1991a, Biochemistry 30, 2306-2310), H54Q, R55A, F60A, Q111A, F113A, and H126Q were assayed for cis-trans peptidyl-prolyl isomerase (PPIase) activity, their ability to bind the immunosuppressive drug cyclosporin A (CsA), and protein phosphatase 2B (calcineurin) inhibition in the presence of CsA. 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