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

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

PROVIDER: PRJNA886067 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21776449_1.fastq.gz	Fastqsanger.gz
	SRR21776449_2.fastq.gz	Fastqsanger.gz
	SRR21776450_1.fastq.gz	Fastqsanger.gz
	SRR21776450_2.fastq.gz	Fastqsanger.gz
	SRR21776451_1.fastq.gz	Fastqsanger.gz

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Coordination of widespread transcription at enhancers and target genes through BRD4

Project description:Coordination of widespread transcription at enhancers and target genes through BRD4

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

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Coordination of widespread transcription at enhancers and target genes through BRD4 (His-NET-Seq)

Project description:Coordination of widespread transcription at enhancers and target genes through BRD4 (His-NET-Seq)

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

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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.

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Project description:We used genome-wide sequencing methods to study stimulus-dependent enhancer function in neurons. We identified ~12,000 neuronal activity-regulated enhancers that are bound by the general transcriptional co-activator CBP in an activity-dependent manner. A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Remarkably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 that is mono-methylated at lysine 4 (H3K4me1). The level of eRNA expression at neuronal enhancers positively correlates with the level of mRNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis. These findings reveal that a widespread mechanism of enhancer activation involves RNAPII binding and eRNA synthesis. Examination of genome-wide binding of three types of modified histones, four transcription factors, and RNA polymerase II (ChIP-Seq), as well as RNA expression (RNA-Seq) before and after membrane depolarization via application of extracellular potassium.

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Coordination of widespread transcription at enhancers and target genes through BRD4

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

2023-07-06 | GSE214594 | GEO