Unbiased clustering revealed gene expression signatures characteristic of older women with skin youthfulness (n = 12) compared to older women without skin youthfulness (n = 33), after accounting for gene expression changes associated with chronological age alone. In vitro, oligomerization leads to pro-caspase processing to from the mature caspase subunits; this processing requires the intrinsic caspase activity of zymogens and proceeds via a novel order of cleavage events. Stem cell regulation and hierarchical organization ofhuman skeletal progenitors remain largely unexplored. Essential for the generation of olfactory and autonomic neurons. View details for DOI 10.1016/j.tcb.2014.06.003, View details for Web of Science ID 000343630000006, View details for PubMedCentralID PMC4177945. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus. The transcription factor PBX3 promotes tumor cell growth through transcriptional suppression of the tumor suppressor p53. View details for DOI 10.1038/s41467-019-11118-8. Gene expression profiles of PNT1a prostate cells expressing FGFR-4 Arg388 or Gly388. Our findings constitute the first identification of a physiological enzymatic activity of SIRT6, and link chromatin regulation by SIRT6 to telomere maintenance and a human premature ageing syndrome. Here, by integrating ultrastructural imaging, long-range optical mapping and computational analysis of whole-genome sequencing, we demonstrate the structure of circular ecDNA. HLF (HLF Transcription Factor, PAR BZIP Family Member) is a Protein Coding gene. 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. SCENICTranscription factor TF Oncogenes are commonly amplified on particles of extrachromosomal DNA (ecDNA) in cancer1,2, but our understanding of the structure of ecDNA and its effect on gene regulation is limited. These results suggest that failure of thymic expression of selective single self-antigens can be sufficient to cause organ-specific autoimmune disease, even in otherwise self-tolerant individuals. In particular, all examined cases of Langerhans cell histiocytosis and histiocytic sarcoma expressed ZBTB46, while all cases of blastic plasmacytoid dendritic cell neoplasm, chronic myelomonocytic leukemia, juvenile xanthogranuloma, Rosai-Dorfman disease, and Erdheim-Chester disease failed to demonstrate expression of ZBTB46. 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. One of the striking regional variations in skin is its pigmentation. Thus, genomic activity of human liver cancers can be decoded by noninvasive imaging, thereby enabling noninvasive, serial and frequent molecular profiling for personalized medicine. RNA structure has important roles in practically every facet of gene regulation, but the paucity of in vivo structural probes limits current understanding. We find variation consistent with lineage bias toward different developmental branches in multipotent cell types. RNA Tm distinguished noncoding versus coding RNAs and identified mRNAs with distinct cellular functions. View details for DOI 10.1158/0008-5472.CAN-05-3115. Fibroblasts are ubiquitous mesenchymal cells with many vital functions during development, tissue repair, and disease. lncRNA-based mechanisms control cell fates during development, and their dysregulation underlies some human disorders caused by chromosomal deletions and translocations. Adapter protein-mediated oligomerization of procaspases is now recognized as a universal mechanism of initiator caspase activation and underlies the control of both cell surface death receptor and mitochondrial cytochrome c-Apaf-1 apoptosis pathways. Most breast cancers expressing the estrogen receptor (ER) are treated successfully with the receptor antagonist tamoxifen (TAM), but many of these tumors recur. Gomez, J. Crystal structure of the N-terminal region of human Ash2L shows a winged-helix motif involved in DNA binding. He, C., Hu, H., Wilson, K. D., Wu, H., Feng, J., Xia, S., Churko, J., Qu, K., Chang, H. Y., Wu, J. C. 7SK-BAF axis controls pervasive transcription at enhancers. View details for DOI 10.1073/pnas.0409462102. The switch from mitosis to meiosis is the key event marking onset of differentiation in the germline stem cell lineage. Because previous clinical trials for triciribine did not include biomarkers of treatment efficacy, this study provides a rationale for revisiting triciribine in the clinical setting as a therapy for patients with breast cancer who overexpress ZNF217. View details for DOI 10.4161/epi.6.5.15221. This locus was defined by crosses between SJL/J and B10.S mice and contains several candidate genes, including NeST. 2010), Virally-transduced fibroblasts(Son EY et. Aire mediates the expression of tissue-specific antigens in thymic epithelial cells to promote tolerance againstself-reactive T lymphocytes. Here we show a critical role for specific recognition of histone H3 trimethylated at lysine 4 (H3K4me3) by the ING4 PHD finger in mediating ING4 gene expression and tumor suppressor functions. The transcription factor PBX3 promotes tumor cell growth through transcriptional suppression of the tumor suppressor p53. RNA structure influences practically every step in the gene expression program. However, if we normalize the corrected data to account for variation among experimental cohorts, a subtle decrease in EDEL Treg cell percentages is revealed and, using the corrected and normalized data, we have redrawn Extended Data Fig. 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. Transcription factor that plays a key role in neuronal differentiation: acts as a pioneer transcription factor, accessing closed chromatin to allow other factors to bind and activate neural pathways. Transcription factor-induced activation of cardiac gene expression in human c-kit+ cardiac progenitor cells has been reported. PHD2 levels are decreased in human cancers, compared with corresponding normal tissue, and correlate with an increase in mature blood vessels. Before The Autoimmune regulator (Aire) gene, which is defective in the disorder autoimmune polyglandular syndrome type 1, has been shown to promote the thymic expression of self-antigens. further dissect the mechanism of regional pigmentation by assessing the effects of dickkopf 1 (DKK1), an antagonist of the Wnt pathway produced in lightly pigmented skin, on melanocyte gene expression. We find that skin aging was associated with a significantly altered expression level of 2,265 coding and noncoding RNAs, of which 1,293 became "rejuvenated" after BBL treatment; i.e., they became more similar to their expression level in youthful skin. Examination of the MASH1 gene in patients with Parkinson's disease. In addition, our data reveal, to our knowledge, a previously unreported set of targets that may lead to new insights into the human skin aging process. DINO was required for p53-dependent gene expression, cell cycle arrest and apoptosis in response to DNA damage, and DINO expression was sufficient to activate damage signaling and cell cycle arrest in the absence of DNA damage. government site. Here we demonstrate that DNA hypomethylation at long terminal repeat elements representing the most recent genomic integrations, together with transactivation by OCT4 (also known as POU5F1), synergistically facilitate HERVK expression. (2017) reveal an additional function of a host-encoded long non-coding RNA (lncRNA) in regulating viral expression by binding a host metabolic enzyme to enhance its catalytic activity. We made a series of discoveries that introduced the important and pervasive roles of long noncoding RNAs in biological regulation. Diseases associated with PRKDC include Immunodeficiency 26 With Or Without Neurologic Abnormalities and Immunodeficiency 26.Among its related pathways are Cytosolic sensors of pathogen-associated DNA and miRNA regulation of DNA damage response.Gene Ontology These results open the door for structural genomics of RNA in living cells and reveal key physiological structures controlling gene expression. After deep sequencing of cDNA, computational analysis yields flexibility scores for every base across the starting RNA population. Here we have identified a polymerase with reverse transcriptase activity (from Thermus thermophilus) that is selective by up to 18-fold for incorporation of thymidine opposite unmodified A over m(6)A. 17beta-estradiol (E2)-regulated gene expression across time in estrogen-dependent and estrogen deprivation-resistant MCF-7-derived breast cancer cell lines. In the current study, we describe the isolation and characterization of a tumor-initiating cell (T-IC) subpopulation in primary human bladder cancer, based on the expression of markers similar to that of normal bladder basal cells (Lineage-CD44(+)CK5(+)CK20(-)). Sudden infant death syndrome: case-control frequency differences at genes pertinent to early autonomic nervous system embryologic development. View details for DOI 10.1016/j.cell.2013.09.028. A., Ortiz-Urda, S., Kretz, M., Garcia, J., Scholl, F. A., Pasmooij, A. M., Cassarino, D., Chang, H. Y., Khavari, P. A. Regeneration, repair and remembering identity: the three Rs of Hox gene expression, Hierarchical Maintenance of MLL Myeloid Leukemia Stem Cells Employs a Transcriptional Program Shared with Embryonic Rather Than Adult Stem Cells. Corces, M. R., Trevino, A. E., Hamilton, E. G., Greenside, P. G., Sinnott-Armstrong, N. A., Vesuna, S. n., Satpathy, A. T., Rubin, A. J., Montine, K. S., Wu, B. n., Kathiria, A. n., Cho, S. W., Mumbach, M. R., Carter, A. C., Kasowski, M. n., Orloff, L. A., Risca, V. I., Kundaje, A. n., Khavari, P. A., Montine, T. J., Greenleaf, W. J., Chang, H. Y. Lineage-specific dynamic and pre-established enhancer-promoter contacts cooperate in terminal differentiation. In multivariate analysis, this signature is not only independent of clinical and pathological risk factors; it is also the strongest predictor of outcome. In particular, genome-wide microarray analysis of differently aged individual organisms or tissues has been used to track the global expression changes that occur during normal aging. Targeted perturbations of cell cycle or transcription factor signalling evoke stimulus-specific changes in this observed variability. The ESC-like transcriptional program is activated in diverse human epithelial cancers and strongly predicts metastasis and death. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of Dino knockout or promoter inactivation in mice dampened p53 signaling and ameliorated acute radiation syndrome in vivo. Here we provide a review of the microarray technology, including the introduction of array platforms, experimental designs, RNA isolation and amplification, array hybridization, and data analysis. Target genes identified with HiChIP are further supported by CRISPR interference and activation at linked enhancers, by the presence of expression quantitative trait loci, and by allele-specific enhancer loops in patient-derived primary cells. Genome-scale expression profiling has identified new subtypes of cancer based on consistent patterns of variation in gene expression, leading to improved prognostic predictions. Protein expression , View details for DOI 10.1016/j.cmet.2016.04.002. Recent advances in SHAPE technology have converted the classic primer extension method to next-generation sequencing platforms, allowing transcriptome-level analysis of RNA secondary structure. 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. In conjunction with DNA transposition, the levels of multiple cell surface or intracellular protein epitopes are recorded by index flow cytometry and positions in arrayed microwells, and then subject to molecular barcoding for subsequent pooled analysis. O'Geen, H., Squazzo, S. L., Iyengar, S., Blahnik, K., Rinn, J. L., Chang, H. Y., Green, R., Farnham, P. J. Patterning skin pigmentation via dickkopf, GSK3 beta mediates suppression of cyclin D2 expression by tumor suppressor PTEN. While emerging studies are greatly expanding the known universe of RNA-binding proteins, methods for the discovery and characterization of protein-RNA interactions remain resource intensive and technically challenging. Using two-photon microscopy, we observed stable antigen-specific interactions between eTACs and autoreactive T cells. View details for DOI 10.1186/s13059-016-0933-0. Cellular differentiation involves profound remodelling of chromatic landscapes, yet the mechanisms by which somatic cell identity is subsequently maintained remain incompletely understood. ASCL1 (Achaete-Scute Family BHLH Transcription Factor 1) is a Protein Coding gene. The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. APEX-seq shouldbe widely applicable to many systems, enabling comprehensive investigations of the spatial transcriptome. Z., Chen, X. n., Gil, I. P., Ameen, M. n., Sallam, K. n., Rhee, J. W., Churko, J. M., Chaudhary, R. n., Chour, T. n., Wang, P. J., Snyder, M. P., Chang, H. Y., Karakikes, I. n., Wu, J. C. Functional significance of U2AF1 S34F mutations in lung adenocarcinomas. 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 mammalian genome contains tens of thousands of long noncoding RNAs (lncRNAs), many of which occur at disease-associated loci or are specifically expressed in cancer. Similarly, human lncRNA HOTAIR can affect PRC2 occupancy on hundreds of genes genome-wide( 3,12,13), but how specificity is achieved is unclear. OIP5-AS1 specifies p53-driven POX transcription regulated by TRPC6 in glioma. However, the molecular architecture of the Xi chromosome, in both the silent and expressed regions,remains unclear. Therefore, RAPs interconnect one of life's most ancient molecular machines with diverse cellular processes, providing an additional layer of regulatory potential to protein expression. 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 UniProtKB/Swiss-Prot, HOMER Transcription Factor Regulatory Elements motif, Enzyme Numbers (IUBMB) , RAMA elements in neural progenitor cells were biallelically accessible in embryonic stem cells but premarked with bivalent histone modifications; one allele was silenced during differentiation. RNA structure is intimately connected to each step of gene expression. Bao, X., Rubin, A. J., Qu, K., Zhang, J., Giresi, P. G., Chang, H. Y., Khavari, P. A. m(6)A RNA Modification Controls Cell Fate Transition in Mammalian Embryonic Stem Cells. Mumbach, M. R., Rubin, A. J., Flynn, R. A., Dai, C., Khavari, P. A., Greenleaf, W. J., Chang, H. Y. Gender was the most significant attributable source of variation. Thus, a precise match between pioneer factors and the chromatin context at key target genes is determinative for transdifferentiation to neurons and likely other cell types. ZYDOWSKY, L. D., Etzkorn, F. A., Chang, H. Y., Ferguson, S. B., STOLZ, L. A., Ho, S. I., Walsh, C. T. CYCLOSPORINE-MEDIATED INHIBITION OF BOVINE CALCINEURIN BY CYCLOPHILIN-A AND CYCLOPHILIN-B. We found that HOXC10 promotes survival in cells treated with doxorubicin, paclitaxel, or carboplatin by suppressing apoptosis and upregulating NF-B Overexpressed HOXC10 increases S-phase-specific DNA damage repair by homologous recombination (HR) and checkpoint recovery in cells at three important phases. My group has substantial experience in epigenetics and RNA biology, including invention of new methods for epigenomic profiling, map RNA occupancy on chromatin, and define RNA structures genome-wide. To better understand these processes, much effort has been put into the study of aging on a molecular level. Using our current knowledge of signaling networks we discuss the role that RNA may play in writing and regulating histone modifications and the information needed for correct gene expression. 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. This gene is overexpressed in Skin (13.0), Oral epithelium (11.8), Esophagus (6.6), and Heart (6.6). This raises the fundamental question of whether lineage reprogramming is possible between cell types derived fromdifferent germ layers. Hox genes encode transcription factors that specify embryonic positional identity in cells and guide tissue differentiation. Because genes work together in groups to carry out specific functions, defining the unit of analysis by coherent changes in biologically meaningful sets of genes, termed modules, improves our understanding of the biological processes underlying the gene expression changes. Mumbach, M. R., Granja, J. M., Flynn, R. A., Roake, C. M., Satpathy, A. T., Rubin, A. J., Qi, Y., Jiang, Z., Shams, S., Louie, B. H., Guo, J. K., Gennert, D. G., Corces, M. R., Khavari, P. A., Atianand, M. K., Artandi, S. E., Fitzgerald, K. A., Greenleaf, W. J., Chang, H. Y. Single-cell lineage tracing by endogenous mutations enriched in transposase accessible mitochondrial DNA. A., Chi, J. The prevention of autoimmunity requires the elimination of self-reactive T cells during their development and maturation. Chu, C., Qu, K., Zhong, F. L., Artandi, S. E., Chang, H. Y. In particular, icSHAPE and SHAPE-MaP, using NAI-N3 and 1M7 reagents, respectively, are methods that claim to measure in vivo structure with high-throughput sequencing. By visualizing genome-scale gene expression in cancer as combinations of activated and deactivated functional modules, gene module maps can reveal specific functional pathways associated with each subtype that might be susceptible to targeted therapies. While the chromatin accessibility landscape of this process has been explored in defined populations, single-cell regulatory variation has been hidden by ensemble averaging. Mazumdar, C., Shen, Y., Xavy, S., Zhao, F., Reinisch, A., Li, R., Corces, M. R., Flynn, R. A., Buenrostro, J. D., Chan, S. M., Thomas, D., Koenig, J. L., Hong, W., Chang, H. Y., Majeti, R. Individuality and Variation of Personal Regulomes in Primary Human T Cells. 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. Diseases associated with ASCL1 include Congenital Central Hypoventilation Syndrome and Central Hypoventilation Syndrome, Congenital, 1.Among its related pathways are Signaling by NTRKs and Nuclear Events (kinase and transcription factor activation).Gene Ontology (GO) All Rights Reserved. UniProtKB/Swiss-Prot, Enzyme Numbers (IUBMB) , These results highlight the potentially broad contribution of RNA structure and its variation to gene regulation. Kawahara, T. L., Rapicavoli, N. A., Wu, A. R., Qu, K., Quake, S. R., Chang, H. Y. RNA templating the epigenome Long noncoding RNAs as molecular scaffolds, A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Here, we computationally identify the sets of human core promoters targeted by motifs, and systematically characterize their function by using a robust gene-set-based approach and diverse sources of biological data. (and/or Entrez Gene and/or Ensembl if different), Santa Cruz Biotechnology (SCBT) Antibodies for HOPX, Taconic Biosciences Mouse Models for HOPX, Santa Cruz Biotechnology (SCBT) CRISPR for HOPX, Santa Cruz Biotechnology (SCBT) siRNA for HOPX, SVs/CNVs around HOPX on UCSC Golden Path with GeneCards custom tracks (. In addition, lack of IRBP expression solely in the thymus, even in the presence of aire expression, is sufficient to trigger spontaneous eye-specific autoimmunity. These results refine concepts of human individuality and provide a foundational reference for comparing disease-associated regulomes. A clear link, however, between specific thymic self-antigens and a single autoimmune phenotype in this model has been lacking. Diseases associated with LOXL2 include Hyperostosis Cranialis Interna and Cutis Laxa.Among its related pathways are Collagen chain trimerization and Elastic fibre formation.Gene Ontology (GO) annotations related to this gene include chromatin binding and electron transfer activity.An important paralog of this Free for academic non-profit institutions.Other users need a Commercial license, The protein encoded by this gene is a homeodomain protein that lacks certain conserved residues required for DNA binding. View details for Web of Science ID 000167056400008. Homeodomain-only protein HOP is a novel modulator of late differentiation in keratinocytes. Furthermore, this is an underestimate of the total RNAs involved in chromatin modification, as PRC2 target genes also transcribe smaller 50-200 nt RNAs that interact with SUZ12 to mediate gene repression[11]. 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. We are particularly fascinated by HOTAIR, the first known lincRNA that can regulate the chromatin state of genes on distantly located chromosomes. We further demonstrate that BAF and p63 cooperatively position nucleosomes away from p63 binding sites and recruit transcriptional machinery to control tissue differentiation.BAF displays high specificity in controlling the open chromatin landscape during epidermal differentiation by cooperating with the master transcription factor p63 to maintain lineage-specific open chromatin regions. gene expression, shRNA knockdown, CRISPR), VectorBuilder Viral vectors for HOPX (ie. Luo, C., Lee, Q., Wapinski, O., Castanon, R., Nery, J. R., Malin, M., Kareta, M. S., Cullen, S. M., Goodell, M. A., Chang, H. Y., Wernig, M., Ecker, J. R. Coupled Single-Cell CRISPR Screening and Epigenomic Profiling Reveals Causal Gene Regulatory Networks. Yost, K. E., Carter, A. C., Xu, J., Litzenburger, U., Chang, H. Y. Epigenomics: Technologies and Applications. These results suggest a systematic approach to understanding the noncoding genome in cancer to advance diagnosis and therapy. View details for DOI 10.1161/CIRCGENETICS.115.001264 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. Zarnegar, B. J., Flynn, R. A., Shen, Y., Do, B. T., Chang, H. Y., Khavari, P. A. Age-Dependent Pancreatic Gene Regulation Reveals Mechanisms Governing Human beta Cell Function. In the past, transcriptomes have largely been parsed by primary sequences and expression levels, but it is now becoming feasible to annotate and compare transcriptomes based on RNA structure. By further characterizing RAPs, we discover the presence of ufmylation, a metazoan-specific post-translational modification (PTM), on ribosomes and define its direct substrates. Caspases are synthesized as inactive precursors termed procaspases; proteolytic processing of procaspase generates the tetrameric active caspase enzyme, composed of two repeating heterotypic subunits. High throughput RNA sequencing of Sezary syndrome and cutaneous squamous cell carcinoma. Atianand, M. K., Hu, W., Satpathy, A. T., Shen, Y., Ricci, E. P., Alvarez-Dominguez, J. R., Bhatta, A., Schattgen, S. A., McGowan, J. D., Blin, J., Braun, J. E., Gandhi, P., Moore, M. J., Chang, H. Y., Lodish, H. F., Caffrey, D. R., Fitzgerald, K. A. irCLIP platform for efficient characterization of protein-RNA interactions. Here we discover and characterize the sets of mouse lncRNAs induced by inflammatory signaling via TNF. Ensembl, locations according to GeneLoc Systematic functional characterization of cis-regulatory motifs in human core promoters. RNA interference (RNAi) is an evolutionarily conserved mechanism in plant and animal cells that directs the degradation of messenger RNAs homologous to short double-stranded RNAs termed small interfering RNA (siRNA). Here we demonstrate that lncRNAs guide the organismal DNA damage response. In tranfected tissue culture cells, FasDelta activated Jun N-terminal kinase normally but was impaired in cell death induction. Oh, S., Flynn, R. A., Floor, S. N., Purzner, J., Martin, L., Do, B. T., Schubert, S., Vaka, D., Morrissy, S., Li, Y., Kool, M., Hovestadt, V., Jones, D. T., Northcott, P. A., Risch, T., Warnatz, H., Yaspo, M., Adams, C. M., Leib, R. D., Breese, M., Marra, M. A., Malkin, D., Lichter, P., Doudna, J. 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 Though overall EZH2 and HOTAIR expression levels were highly correlated, the subset of cases with strong HOTAIR expression correlated with ER and PR positivity, while the subset of cases with strong EZH2 expression correlated with an increased proliferation rate, ER and PR negativity, HER2 underexpression, and triple negativity. We examined ZBTB46 expression in a range of benign and malignant histiocytic disorders and found that ZBTB46 is able to clearly define the dendritic cell identity of many previously unclassified histiocytic disease subtypes. PANDA interacts with the transcription factor NF-YA to limit expression of pro-apoptotic genes; PANDA depletion markedly sensitized human fibroblasts to apoptosis by doxorubicin. SFRP2 (Secreted Frizzled Related Protein 2) is a Protein Coding gene. The Supplementary Information to this Amendment contains the corrected and reanalysed Extended Data Fig. We also point out the limits of current methods and discuss potential directions for future improvements. p38 mapmapk Mice deficient for caspase genes have highlighted tissue- and signal-specific pathways for apoptosis and demonstrated an independent function for caspase-1 and -11 in cytokine processing. Simsek, D., Tiu, G. C., Flynn, R. A., Byeon, G. W., Leppek, K., Xu, A. F., Chang, H. Y., Barna, M. Generation of pure GABAergic neurons by transcription factor programming. The miR-34a/WNT7B modulates the sensitivity of cholangiocarcinoma cells to p53-mediated photodynamic therapy toxicity. For each archetype, examples from several disparate biological contexts illustrate the commonality of the molecular mechanisms, and these mechanistic views provide useful explanations and predictions of biological outcomes. HLF (HLF Transcription Factor, PAR BZIP Family Member) is a Protein Coding gene. Using a mouse hybrid F1 system, we found that monoallelic DNA accessibility across autosomes was pervasive, developmentally programmed and composed of several patterns. Genomic analysis of Treg cells by RNA-sequencing, Foxp3 chromatin immunoprecipitation followed byhigh-throughput DNA sequencing (ChIP-sequencing), and H3K27ac-HiChIP revealed a specific de-repression of the Th2 transcriptional program leading to the generation of Th2-like Treg cells that were unable to suppress extrinsic Th2 cells. Overall, this work provides a framework for integrative exploration of complex regulatory dynamics in a primary human tissue at single-cell resolution. Flynn, R. A., Do, B. T., Rubin, A. J., Calo, E., Lee, B., Kuchelmeister, H., Rale, M., Chu, C., Kool, E. T., Wysocka, J., Khavari, P. A., Chang, H. Y. Integrative genomic analysis by interoperation of bioinformatics tools in GenomeSpace. Rejuvenated genes (RGs) included several known key regulators of organismal longevity and their proximal long noncoding RNAs. Protein differential expression in normal tissues , Long noncoding RNAs (lncRNAs) are a pervasive and recently recognized class of genes. TRAIL and taurolidine enhance the anticancer activity of doxorubicin, trabectedin and mafosfamide in human fibrosarcoma cells. Sun, L., Fazal, F. M., Li, P., Broughton, J. P., Lee, B., Tang, L., Huang, W., Kool, E. T., Chang, H. Y., Zhang, Q. RNA structure maps across mammalian cellular compartments. Advertising prices for 2023 are available on, Gastric GIST: Risk of Disease Progression (, Copyright PathologyOutlines.com, Inc. Click, 30100 Telegraph Road, Suite 408, Bingham Farms, Michigan 48025 (USA). For instance, Drosophila lncRNAs roX1 and roX2 bind numerous regions on the X chromosome of male cells, and are critical for dosage compensation (10,11). PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit) is a Protein Coding gene. We have previously reported on biological hypothesis-driven analysis of gene expression profiling data and we wished to extend this approach through the combinations of various gene signatures to improve the prediction of outcome in breast cancer.We have used gene expression data (25.000 gene probes) from a previously published study of tumours from 295 early stage breast cancer patients from the Netherlands Cancer Institute using updated follow-up. Comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-ms) is a novel technique for studying endogenous ribonucleoprotein complexes. These two factors are regulated by PHD2 in a HIF-independent but NF-kappaB-dependent manner. During both embryonic development and adult tissue regeneration, changes in chromatin structure driven by master transcription factors lead to stimulus-responsive transcriptional programs. Satb1 integrates DNA binding site geometry and torsional stress to differentially target nucleosome-dense regions. Comparison of native deproteinized RNA isolated from cells versus refolded purified RNA suggests that the majority of the RSS information is encoded within RNA sequence. View details for DOI 10.1111/j.0022-202X.2005.23827.x. 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. Yamaguchi et al. We utilized a novel G228W-knockin mouse model to show that this variant acted in a dominant-negative manner to cause a unique autoimmunity syndrome. ChIRP-MS analysis of four ncRNAs captures key protein interactors, including a U1-specific link to the 3' RNA processing machinery. BMPs and their antagonists are known to play a crucial role in stem and progenitor cell biology as regulators of the balance between expansion and differentiation. Because KAP1 is recruited to the DNA via interaction with KRAB-ZNF proteins, we suggest that expression of KRAB-ZNF genes may be controlled via an auto-regulatory mechanism involving KAP1. New technologies that enable enumeration of lncRNA interaction partners and determination of lncRNA structure are well positioned to drive deeper understanding of their functions and involvement in pathogenesis. These SMS-like phenotypes are produced by loss of Rai1 function in distinct neuronal types: Rai1 loss in inhibitory neurons or subcortical glutamatergic neurons causes learning deficits, while Rai1 loss in Sim1(+) or SF1(+) cells causes obesity. 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 DNA damage induces five lncRNAs from the CDKN1A promoter, and one such lncRNA, named PANDA, is induced in a p53-dependent manner. Recent progress suggests that the involvement of lncRNAs in human diseases could be far more prevalent than previously appreciated. Our results uncover the multifaceted role of DDX21 in multiple steps of ribosome biogenesis, and provide evidence implicating a mammalian RNA helicase in RNA modification and Pol II elongation control. Interacts with serum response factor (SRF). Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. We identify 216 transcribed regions that encode putative lncRNAs, many with RT-PCR-validated periodic expression during the cell cycle, show altered expression in human cancers and are regulated in expression by specific oncogenic stimuli, stem cell differentiation or DNA damage. In matched primary and metastatic cancers, both HOTAIR and EZH2 had increased expression in the metastatic carcinomas. The Daxx-ASK1 connection completes a signaling pathway from a cell surface death receptor to kinase cascades that modulate nuclear transcription factors. A., Qu, K., Georgiev, P., Chu, C., Akhtar, A., Chang, H. Y. Modeling Inducible Human Tissue Neoplasia Identifies an Extracellular Matrix Interaction Network Involved in Cancer Progression. The overall survival at 15 years for patients with tumours in groups 1, 2 and 3 are 79%, 59% and 27%, respectively. Duren, Z., Chen, X., Zamanighomi, M., Zeng, W., Satpathy, A. T., Chang, H. Y., Wang, Y., Wong, W. H. An Activity Switch in Human Telomerase Based on RNA Conformation and Shaped by TCAB1. Yet very little is known about specific genes involved in this complex skin disease, and the underlying molecular mechanisms are not fully understood.We used human DNA microarrays to identify a molecular picture of the programmed responses of the human genome to AE. Thus, numerous lncRNAs may be modulated as a class in development and disease, notably where Dcr and cMyc act. A., Qu, K., Georgiev, P., Chu, C., Alchtar, A., Chang, H. Y. Dicer-microRNA-Myc circuit promotes transcription of hundreds of long noncoding RNAs. Quantitative trait loci mapping confirmed linkage disequilibrium. View details for DOI 10.1016/j.stem.2011.09.002. CRISPR, shRNA, barcode), VectorBuilder BAC recombineering for HOPX, LipExoGen Custom Lentivirus Services - Fast Turnaround - shRNA, sgRNA, miRNA, cDNA, and reporters (TFs, signal pathway, gene promoter), VectorBuilder Stable cell line generation for HOPX, HOPX CRISPR Engineered iPSC Disease Model, Contact an Expert about Cell Line Engineering, HyStem+TGFbeta3+GDF5-induced 7PEND24 cells, HyStem+TGFbeta3+GDF5-induced 4D20.8 cells(Sternberg H et. 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. A Long Noncoding RNA lincRNA-EPS Acts as a Transcriptional Brake to Restrain Inflammation. View details for DOI 10.1016/j.tcb.2009.03.007. SPI1 (Spi-1 Proto-Oncogene) is a Protein Coding gene. Furthermore, factors that interact with lncRNAs in this process are not well characterized.-Utilizing RNA sequencing, we systematically define the contrasting lncRNA expression patterns between fetal and adult heart. To overcome these limitations, we have developed a rapid and large-scale approach to characterize binding of in vitro transcribed labeled RNA to ~9,400 human recombinant proteins spotted on protein microarrays.We have optimized methodology to probe human protein microarrays with full-length RNA molecules and have identified 137 RNA-protein interactions specific for 10 coding and non-coding RNAs. View details for Web of Science ID 000253766700014, View details for PubMedCentralID PMC2259112. In order to dissect the genetic background several linkage and genetic association studies have been performed. Diseases associated with LOXL2 include Hyperostosis Cranialis Interna and Cutis Laxa.Among its related pathways are Collagen chain trimerization and Elastic fibre formation.Gene Ontology (GO) annotations related to this gene include chromatin binding and electron transfer activity.An important paralog of this Effect of Genetic Variant in miR-196a-2 in MCF-7 cells, Gene expression changes in PBMCs from metabolic syndrome patients after acute intake of phenol-rich virgin olive oil, Down-regulation of SFRP1 in a mammary epithelial cell line, Effect of heteronemin on gene expression profiles in chronic myelogenous K562 leukemia cells, miR-17 seed family specific targets in two Hodgkin lymphoma cell lines, Activation of Host Wound Responses in Breast Cancer Microenvironment, Multiomics study to identify virulence factors of Rickettsia prowazekii revealed its adaptive mutation capabilities, Scavenger receptor B2 is a cellular receptor for enterovirus 71, Endometrial gene expression analysis at the time of embryo implantation in women with unexplained infertility, Laughter specific genes and laughter sensitive genes, Human keratinocytes exposed to tungsten carbide and tungsten carbide cobalt nanoparticles and cobalt chloride, Molecular characterization of head and neck cancer cell model genomes, Comparative transcription profiling of peripheral blood mononuclear cells from vasculitis patients, Iodide effect on mRNA expression levels of genes related to immunological function in cultured human thyroid follicles, Detection of Treatment-Induced Changes in Signaling Pathways in GI Stromal Tumors using Transcriptomic Data, Runx1 (Aml1) knockdown in AMkL Meg-01 cells, Multiple platform assessment of the EGF dependent transcriptome by microarray and deep tag sequencing analysis, The kinase TNIK is an essential activator of Wnt target genes, HER2-positive breast cancer cells resistant to trastuzumab and lapatinib lose reliance upon HER2 and are sensitive to the multitargeted kinase inhibitor sorafenib, BxPC-3 cells: growth in different nutrients, Impact of RNA degradation on gene expression profiling, Human osteoblast treated with chemotherapy-treated bone marrow stromal cell conditioned media, Human osteoblast treated with recombinant TGF-beta, Expression profiles of human osteoblasts directly and indirectly damaged by chemotherapy, Genome-Wide Expression Profiling Deciphers Host Responses Altered during Dengue Shock Syndrome and Reveals the Role of Innate Immunity in Severe Dengue, Effects of dexamethasone on human skeletal muscle and adipose tissue, Control vs. HMEC-1 cells treated with 100ng/ml TNF-alpha for 4h and 24h, Propionibacterium acnes as a frequent inflammatory agent involved in prostate cancer, Identification of LATS transcriptional targets in HeLa cells using whole human genome oligonucleotide micorarray, Genopal: a novel platform for focused microarray analysis, Effects of retinoids on estrogen-receptor-positive and -negative breast carcinoma cells: mRNA profiling, Over-expression of hsa-miR-221 in JSC1 cells and identification of miRNA targets expressed in a panel of B-cell lines, Transcription repression of miR-221 leads to p27 expression in PEL, ChIP-chip from HCT116 cells treated with MMS and LNCaP cells with ATF3, Expression profiles of epicardial and subcutaneous adipose tissue, Genes regulated by high calcium medium in parathyroid tissue explants from patients with primary hyperparathyroidism, Effects of retinoids on estrogen-receptor-positive and -negative breast carcinoma cells: mRNA and miRNA profiling, Chronic Active B Cell Receptor Signaling in Diffuse Large B Cell Lymphoma, Expression consequences of decoy vs scrambled oligonucleotides harboring AAAA[AGT]TT motif in MBA-MD-231 cell line, ELK1 and NFYA knockdown in MBA-MD-231 cell line, Decoy vs Scrambled and siRNA vs Mock Transfected MBA-MD-231 Cell Line, Control of gene expression by the Retinoic acid-related Orphan Receptor alpha in HepG2 human hepatoma cells, Effect of exercise on gene expression profile in unfractionated peripheral blood leukocytes, Human primary subcutaneous preadipocytes: Control vs PBMC co-culture, Dissection of human fibroblast populations by lung regions: genomic differences and functional pathway analysis, Subcutaneous adipose tissue (SAT) gene expression patterns between weight control and regaining weight subjects, BRCA1 Haploinsufficiency Leads to Altered Expression of Genes Involved in Cellular Proliferation and Development, Identification of LY6K target genes in bladder cancer, Gene expression profiles of bladder cancer cell lines, Identification of miR-145 or miR-133a target genes in bladder cancer, Identification of miR-489 or miR-504 target genes in head and neck cancer, Gene expression profile of fresh human acute myeloid leukemia cells exposed ex vivo to AS602868, Effect of valproic acid on hematopoiesis: A functional profiling and cell phenotyping approach, Gene expression profiles of oxaliplatin resistant colorectal cancer and ovarian cancer cell lines, Identification of miR-145 or miR-133a target genes in squamous cell carcinoma, Direct generation of induced pluripotent stem cells from human non-mobilized blood, Bifidobacterium bifidum BF-1 Suppresses Helicobacter pylori-Induced genes in Human Epithelial Cells, A Gene Expression Signature for Chemoradiosensitivity of Colorectal Cancer Cells, Identification of cis- and trans-acting factors involved in the localization of MALAT-1 to nuclear speckles, Whole Blood Cell Gene Expression Profiling in Patients with Coronary Artery Disease from the Cathgen Registry, Whole Blood Cell Gene Expression Profiling in Patients with Coronary Artery Disease from the PREDICT Trial, Whole Blood Cell Gene Expression Profiling in Patients with Coronary Artery Disease (Homo sapiens), Efficacy of anti-TNF biologic agent, infliximab, for RA patients using transcriptome analysis of white blood cells, Gene expression signatures for human iPS cell lines, Mutated KRAS induces overexpression of DUSP4, a MAP-kinase phosphatase, and SMYD3, a histone methyltransferase, in rectal carcinomas. 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