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BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire

ABSTRACT: BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire

PROVIDER: PRJNA324572 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3631720.fastq.gz	Fastqsanger.gz
	SRR3631730.fastq.gz	Fastqsanger.gz
	SRR3632000.fastq.gz	Fastqsanger.gz
	SRR3632010.fastq.gz	Fastqsanger.gz
	SRR3632020.fastq.gz	Fastqsanger.gz

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BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire.

Project description:Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4.

| S-EPMC5224504 | biostudies-literature

BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire [ChIP-Seq]

Project description:We examined context specific function of BRD4 in promoting lineage specific gene expression and show that BRD4 is essential for osteoblast differentiation.

2016-10-04 | GSE82295 | GEO

BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire [mRNA-Seq]

Project description:We examined context specific function of BRD4 in promoting lineage specific gene expression and show that BRD4 is essential for osteoblast differentiation.

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BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-10-04 | GSE82297 | GEO

Brd4 and JMJD6-associated Anti-pause Enhancers in Regulation of Transcriptional Pause Release

Project description:Distal enhancers characterized by H3K4me1 mark play critical roles in developmental and transcriptional programs. However, potential roles of specific distal regulatory elements in regulating RNA Polymerase II (Pol II) promoter-proximal pause release remain poorly investigated. Here we report that a unique cohort of jumonji C domain-containing protein 6 (JMJD6) and bromodomain-containing protein 4 (Brd4) co-bound distal enhancers, termed anti-pause enhancers (A-PEs), regulate promoter-proximal pause release of a large subset of transcription units via long-range interactions. Brd4-dependent JMJD6 recruitment on A-PEs mediates erasure of H4R3me2(s), which is directly read by 7SK snRNA, and decapping/demethylation of 7SK snRNA, ensuring the dismissal of the 7SKsnRNA/HEXIM inhibitory complex. The interactions of both JMJD6 and Brd4 with the P-TEFb complex permit its activation and pause release of regulated coding genes. The functions of JMJD6/ Brd4-associated dual histone and RNA demethylase activity on anti-pause enhancers have intriguing implications for these proteins in development, homeostasis and disease. All Gro-seq(s) were designed to reveal the transcriptional targets of JMJD6 and Brd4, and assess the role of JMJD6 and Brd4 in Pol II promoter-proximal pause release. All ChIP-seq(s) were designed to understand the unique features, associated molecular mechanisms and functions of the anti-pause enhancers (A-PEs) discovered in the current study.

2014-01-14 | E-GEOD-51633 | biostudies-arrayexpress

Distinct roles of Brd2 and Brd4 in potentiating the transcriptional program for Th17 cell differentiation

Project description:We analyzed the genome wide distributions of Brd2 and Brd4 in Th17 cells. We find that Brd2 and Brd4 have distinct genome-wide localization in Th17 cells, further experiments reveal tht Brd2 faciliates TF-complex formation in enhancers, enhancer-promoter interaction while Brd4 enhances transcriptional elongation.

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Coordination of widespread transcription at enhancers and target genes through BRD4 (HiChIP)

Project description:Gene transcription by RNA polymerase II (Pol II) is under the control of promoters and distal regulatory elements known as enhancers. Enhancers are themselves transcribed by Pol II which correlates with their activity. How enhancer transcription is regulated and coordinated with transcription at target genes has remained unclear. Here, we developed a high-sensitive native elongating transcript sequencing approach, called HiS-NET-seq, to provide an extended high-resolution view on transcription, especially at lowly transcribed regions such as enhancers. HiS-NET-seq uncovers new transcriptional enhancers in human cells. An integrated multi-omics analysis shows that transcription at most enhancers depends on the BET protein BRD4. We provide evidence for a direct BRD4-mediated coupling of Pol II transcription at enhancers and target genes. Specifically, BRD4 links elongation activation at enhancers and genes by maintaining their proximity. These studies reveal that transcription at enhancers and target genes is coordinated at the level of elongation.

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NF-kB coordinates rapid, BRD4-dependent remodeling of proinflammatory super-enhancers [Affymetrix]

Project description:Proinflammatory stimuli rapidly and globally remodel chromatin landscape, thereby enabling transcriptional responses. Yet, the mechanisms coupling chromatin regulators to the master regulatory inflammatory transcription factor NF-kB remain poorly understood. We report in human endothelial cells (ECs) that activated NF-kB binds to enhancers, provoking a rapid, global redistribution of BRD4 preferentially at super-enhancers, large enhancer domains highly bound by chromatin regulators. Newly established NF-kB super-enhancers drive nearby canonical inflammatory response genes. In both ECs and macrophages BET bromodomain inhibition prevents super-enhancer formation downstream of NF-kB activation, abrogating proinflammatory transcription. In TNFa-activated endothelium this culminates in functional suppression of leukocyte rolling, adhesion and transmigration. Sustained BET bromodomain inhibitor treatment of LDLr -/- animals suppresses atherogenesis, a disease process rooted in pathological vascular inflammation involving endothelium and macrophages. These data establish BET-bromodomains as key effectors of inflammatory response through their role in the dynamic, global reorganization of super-enhancers during NF-kB activation. Gene expression analysis of human endothelial cells in resting state, treatment with TNFalpha or TNFalpha with the BET bromodomain inhibitor JQ1

2014-09-29 | E-GEOD-53999 | biostudies-arrayexpress

Coordination of widespread transcription at enhancers and target genes through BRD4 (ChIP-Rx)

2023-07-06 | GSE214590 | GEO

BRD4 is necessary for epidermal differentiation

Project description:BRD4 is an epigenetic reader known to bind to acetylated lysines on histones and transcription factors, and it has been implicated in recruiting transcriptional machinery to promote differentiation gene expression in multiple cellular contexts. This activity is dependant on proper BRD4 localization to active promoters and enhancers, which is dependant on a variety of factors including lineage determining transcription factors (LDTFs). We found BRD4 to be necessary for epidermal differentiation, during which it shares many chromatin binding sites with a variety of epidermal lineage-determining transcription factors (LDTF's). BRD4 also regulates a similar differentiation related transcriptional program with the epidermal LDTF KLF4.

2020-04-03 | GSE140992 | GEO

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