Article ; Online: High-sensitive nascent transcript sequencing reveals BRD4-specific control of widespread enhancer and target gene transcription.
2023 Volume 14, Issue 1, Page(s) 4971
Abstract: 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 ... ...
| Abstract | 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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| MeSH term(s) | Humans ; Nuclear Proteins/genetics ; Transcription Factors/genetics ; Regulatory Sequences, Nucleic Acid ; RNA Polymerase II/genetics ; Transcription, Genetic ; Cell Cycle Proteins/genetics |
| Chemical Substances | Nuclear Proteins ; Transcription Factors ; RNA Polymerase II (EC 2.7.7.-) ; BRD4 protein, human ; Cell Cycle Proteins |
| Language | English |
| Publishing date | 2023-08-17 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2553671-0 |
| ISSN | 2041-1723 ; 2041-1723 |
| ISSN (online) | 2041-1723 |
| ISSN | 2041-1723 |
| DOI | 10.1038/s41467-023-40633-y |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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