Promoter-specific changes in initiation, elongation and homeostasis of histone H3 acetylation during CBP/p300 inhibition

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Abstract

Regulation of RNA Polymerase II (Pol2) elongation in the promoter proximal region is an important and ubiquitous control point for gene expression in metazoans. We report that transcription of the adenovirus 5 E4 region is regulated during the release of paused Pol2 into productive elongation by recruitment of the super elongation complex (SEC), dependent on promoter H3K18/27 acetylation by CBP/p300. We also establish that this is a general transcriptional regulatory mechanism that applies to ~6% of expressed protein-coding genes in primary human airway epithelial cells. We observed that a homeostatic mechanism maintains promoter, but not enhancer H3K18/27ac in response to extensive inhibition of CBP/p300 acetyl transferase activity by the highly specific small molecule inhibitor A-485. Further, our results suggest a function for BRD4 association at enhancers in regulating paused Pol2 release at nearby promoters. Taken together, our results uncover processes regulating transcriptional elongation by promoter region histone H3 acetylation and homeostatic maintenance of promoter, but not enhancer, H3K18/27ac in response to inhibition of CBP/p300 acetyl transferase activity.

Data availability

Sequencing data have been deposited in GEO under accession code GSE167094.

The following data sets were generated

1. Arnold J Berk
(2021) Promoter-specific changes in initiation, elongation and homeostasis of histone H3 acetylation during CBP/p300 Inhibition
NCBI Gene Expression Omnibus, GSE167094.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE167094

Article and author information

Author details

Emily Hsu

Molecular Biology Institute, UCLA, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Nathan R Zemke

Molecular Biology Institute, UCLA, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6326-5925
Arnold J Berk

Molecular Biology Institute, UCLA, Los Angeles, United States

For correspondence
arnold.berk@icloud.com

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9379-6287

Funding

Professor June Lascelle Fund

Arnold J Berk

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.