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

Annkatrin Bressin, Olga Jasnovidova, Mirjam Arnold, Elisabeth Altendorfer, Filip Trajkovski, Thomas A. Kratz, Joanna E. Handzlik, Denes Hnisz and Andreas Mayer ()
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Annkatrin Bressin: Max Planck Institute for Molecular Genetics
Olga Jasnovidova: Max Planck Institute for Molecular Genetics
Mirjam Arnold: Max Planck Institute for Molecular Genetics
Elisabeth Altendorfer: Max Planck Institute for Molecular Genetics
Filip Trajkovski: Max Planck Institute for Molecular Genetics
Thomas A. Kratz: Max Planck Institute for Molecular Genetics
Joanna E. Handzlik: Max Planck Institute for Molecular Genetics
Denes Hnisz: Max Planck Institute for Molecular Genetics
Andreas Mayer: Max Planck Institute for Molecular Genetics

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-40633-y

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