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Coordination of widespread transcription at enhancers and target genes through BRD4

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE214594 | GEO | 2023/07/06

REPOSITORIES: GEO

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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.

2023-07-06 | GSE214591 | GEO

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)

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

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

Project description: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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Transcription factor p63 bookmarks genomic loci in epithelial cells and regulates a subset of target genes during epidermal differentiation through dynamic enhancers

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Widespread transcription at neuronal activity-regulated enhancers.

Project description:We used genome-wide sequencing methods to study stimulus-dependent enhancer function in mouse cortical neurons. We identified approximately 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. Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of eRNA expression at neuronal enhancers positively correlates with the level of messenger RNA 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.

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High-sensitive nascent transcript sequencing reveals BRD4-specific control of widespread enhancer and target gene transcription.

Project description:Gene transcription by RNA polymerase II (Pol II) is under control of promoters and distal regulatory elements known as enhancers. Enhancers are themselves transcribed by Pol II correlating 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 transcribed enhancers in human cells. A multi-omics analysis shows that genome-wide enhancer transcription depends on the BET family protein BRD4. Specifically, BRD4 co-localizes to enhancer and promoter-proximal gene regions, and is required for elongation activation at enhancers and their genes. BRD4 keeps a set of enhancers and genes in proximity through long-range contacts. From these studies BRD4 emerges as a general regulator of enhancer transcription that may link transcription at enhancers and genes.

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