Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA111107 | ENA |
REPOSITORIES: ENA
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Project description:ChIP-on-chip has emerged as a powerful tool to dissect the complex network of regulatory interactions between transcription factors and their targets. However, most ChIP-on-chip analysis methods use conservative approaches aimed to minimize false-positive transcription factor targets. We present a model with improved sensitivity in detecting binding events from ChIP-on-chip data. Its application to human T-cells, followed by extensive biochemical validation, reveals that three transcription factor oncogenes, NOTCH1, MYC, and HES1, bind to several thousands target gene promoters, up to an order of magnitude increase over conventional analysis methods. Gene expression profiling upon NOTCH1 inhibition shows broad-scale functional regulation across the entire range of predicted target genes, establishing a closer link between occupancy and regulation. Finally, the increased sensitivity reveals a combinatorial regulatory program in which MYC co-binds to virtually all NOTCH1-bound promoters. Overall, these results suggest an unappreciated complexity of transcriptional regulatory networks and highlight the fundamental importance of genome-scale analysis to represent transcriptional programs.
2008-12-04 | GSE12868 | GEO
Project description:ChIP-on-chip has emerged as a powerful tool to dissect the complex network of regulatory interactions between transcription factors and their targets. However, most ChIP-on-chip analysis methods use conservative approaches aimed to minimize false-positive transcription factor targets. We present a model with improved sensitivity in detecting binding events from ChIP-on-chip data. Its application to human T-cells, followed by extensive biochemical validation, reveals that three transcription factor oncogenes, NOTCH1, MYC, and HES1, bind to several thousands target gene promoters, up to an order of magnitude increase over conventional analysis methods. Gene expression profiling upon NOTCH1 inhibition shows broad-scale functional regulation across the entire range of predicted target genes, establishing a closer link between occupancy and regulation. Finally, the increased sensitivity reveals a combinatorial regulatory program in which MYC co-binds to virtually all NOTCH1-bound promoters. Overall, these results suggest an unappreciated complexity of transcriptional regulatory networks and highlight the fundamental importance of genome-scale analysis to represent transcriptional programs. Experiment Overall Design: T-ALL cell lines harboring activating mutations in NOTCH1 were treated with vehicle only (DMSO) or a highly active gamma-secretase inhibitor (COMPE, 100nM) for 72 hs and processed for gene expression profiling analysis. Gene expression signatures associated with inhibition of NOTCH1 signaling with CompE were correlated with findings on NOTCH1 direct target genes identified by ChIP-on-chip analysis.
2008-12-12 | E-GEOD-12868 | biostudies-arrayexpress
Project description:Duplication of genes encoding transcription factors plays an essential role in driving phenotypic variation. Because regulation can occur at multiple levels, it is often difficult to discern how each duplicated factor achieves its regulatory specificity. In these cases, a systems approach may distinguish the role of each factor by integrating complementary large-scale measurements of the regulatory network. To explore such an approach, we integrate growth phenotypes, promoter binding profiles, and gene expression patterns to model the DNA damage response network controlled by the Yeast-specific AP-1 (YAP) family of transcription factors. This analysis reveals that YAP regulatory specificity is achieved by at least three mechanisms: (a) Divergence of DNA-binding sequences into two subfamilies; (b) Condition-specific combinatorial regulation by multiple Yap factors; and (c) Interactions of Yap 1, 4, and 6 with chromatin remodeling proteins. Additional microarray experiments establish that Yap4 and 6 regulate gene expression through interactions with the histone deacetylase, Hda1. The data further highlight differences among Yap paralogs in terms of their regulatory mode of action (activation vs. repression). This study suggests how other large TF families might be disentangled in the future. Keywords: gene expression microarray and ChIP-chip Gene expression of wild type and single YAP deletion (YAP1/2/4/5/6) strains were profiled in media supplemented with either MMS or CDDP at two different concentrations. ChIP-chip of five YAPs (YAP1/2/4/6/6) were done in duplicate in both drug-treated (MMS or CDDP) or untreated (SC media) conditions.
2008-02-03 | E-GEOD-10146 | biostudies-arrayexpress
Project description:Nucleosome driven transcription factor binding and gene regulation [ChIP-Seq]
| PRJNA177082 | ENA
Project description:Duplication of genes encoding transcription factors plays an essential role in driving phenotypic variation. Because regulation can occur at multiple levels, it is often difficult to discern how each duplicated factor achieves its regulatory specificity. In these cases, a systems approach may distinguish the role of each factor by integrating complementary large-scale measurements of the regulatory network. To explore such an approach, we integrate growth phenotypes, promoter binding profiles, and gene expression patterns to model the DNA damage response network controlled by the Yeast-specific AP-1 (YAP) family of transcription factors. This analysis reveals that YAP regulatory specificity is achieved by at least three mechanisms: (a) Divergence of DNA-binding sequences into two subfamilies; (b) Condition-specific combinatorial regulation by multiple Yap factors; and (c) Interactions of Yap 1, 4, and 6 with chromatin remodeling proteins. Additional microarray experiments establish that Yap4 and 6 regulate gene expression through interactions with the histone deacetylase, Hda1. The data further highlight differences among Yap paralogs in terms of their regulatory mode of action (activation vs. repression). This study suggests how other large TF families might be disentangled in the future. Keywords: gene expression microarray and ChIP-chip
2008-02-04 | GSE10146 | GEO
Project description:In many cancers, critical oncogenes are driven from large regulatory elements, called super-enhancers, which recruit much of the cellM-bM-^@M-^Ys transcriptional apparatus and are defined by extensive H3K27 acetylation. We found that in T-cell acute lymphoblastic leukemia (T-ALL), somatic heterozygous mutations introduce MYB binding motifs in a precise noncoding site, which nucleate a super-enhancer upstream of the TAL1 oncogene. Further analysis of genome-wide binding identified MYB and its histone acetylase binding partner CBP as core components of the TAL1 complex and of the TAL1-mediated feed-forward auto-regulatory loop that drives T-ALL. Furthermore, MYB and CBP occupy endogenous MYB binding sites in the majority of super-enhancer sites found in T-ALL cells. Thus, our study reveals a new mechanism for the generation of super-enhancers in malignant cells involving the introduction of somatic indel mutations within non-coding sequences, which introduce aberrant binding sites for the MYB master transcription factor. ChIP-Seq for transcription factors and co-factors in T cell acute lymphoblastic leukemia cell lines
2014-11-13 | E-GEOD-59657 | biostudies-arrayexpress
Project description:Increasing evidence suggests that transcriptional control and chromatin activities at large involve regulatory RNAs, which likely enlist specific RNA binding proteins (RBPs). Although multiple RBPs have been implicated in transcriptional control, it has remained unclear how extensively RBPs directly act on chromatin. We embarked on a large-scale RBP ChIP-seq analysis, revealing widespread RBP presence in active chromatin regions in the human genome. Like transcription factors (TFs), RBPs also showed strong preference for hotspots in the genome, particularly gene promoters, where their association is frequently linked to transcriptional output. Unsupervised clustering reveals extensive co-association between TFs and RBPs, as exemplified by YY1, a known RNA-dependent TF, and RBM25, an RBP involved in splicing regulation. Remarkably, RBM25 depletion attenuates all YY1-dependent activities, including chromatin binding, DNA looping and transcription. We propose that various RBPs may enhance network interaction through harnessing regulatory RNAs to control transcription. As part of the ENCODE consortium, we embarked on a large-scale RBP ChIP-seq analysis, revealing broad presence of RBPs in active chromatin regions in the human genome. Like transcription factors (TFs), RBPs also show great preference for hotspots in the genome, particularly gene promoters, where their binding is frequently linked to transcriptional output. Self-organizing map reveals extensive co-binding events between TFs and RBPs, as exemplified by those between YY1, a known RNA-dependent TF, and RBM25, an RBP involved in alternative splicing. Remarkably, RBM25 depletion attenuates all YY1-dependent activities, including chromatin binding, DNA looping and transcription. We propose that various RBPs may bridge specific TF-RNA interactions to control transcription.
2019-06-27 | GSE120105 | GEO
Project description:Increasing evidence suggests that transcriptional control and chromatin activities at large involve regulatory RNAs, which likely enlist specific RNA binding proteins (RBPs). Although multiple RBPs have been implicated in transcriptional control, it has remained unclear how extensively RBPs directly act on chromatin. We embarked on a large-scale RBP ChIP-seq analysis, revealing widespread RBP presence in active chromatin regions in the human genome. Like transcription factors (TFs), RBPs also showed strong preference for hotspots in the genome, particularly gene promoters, where their association is frequently linked to transcriptional output. Unsupervised clustering reveals extensive co-association between TFs and RBPs, as exemplified by YY1, a known RNA-dependent TF, and RBM25, an RBP involved in splicing regulation. Remarkably, RBM25 depletion attenuates all YY1-dependent activities, including chromatin binding, DNA looping and transcription. We propose that various RBPs may enhance network interaction through harnessing regulatory RNAs to control transcription.
2019-06-27 | GSE120104 | GEO
Project description:Increasing evidence suggests that transcriptional control and chromatin activities at large involve regulatory RNAs, which likely enlist specific RNA binding proteins (RBPs). Although multiple RBPs have been implicated in transcriptional control, it has remained unclear how extensively RBPs directly act on chromatin. We embarked on a large-scale RBP ChIP-seq analysis, revealing widespread RBP presence in active chromatin regions in the human genome. Like transcription factors (TFs), RBPs also showed strong preference for hotspots in the genome, particularly gene promoters, where their association is frequently linked to transcriptional output. Unsupervised clustering reveals extensive co-association between TFs and RBPs, as exemplified by YY1, a known RNA-dependent TF, and RBM25, an RBP involved in splicing regulation. Remarkably, RBM25 depletion attenuates all YY1-dependent activities, including chromatin binding, DNA looping and transcription. We propose that various RBPs may enhance network interaction through harnessing regulatory RNAs to control transcription.
2019-06-27 | GSE120023 | GEO
Project description:Genome-scale Analysis of E. coli FNR Reveals Complex Features of Transcription Factor Binding
| PRJNA176146 | ENA