Promoter-specific changes in initiation, elongation, and homeostasis of histone H3 acetylation during CBP/p300 inhibition
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 rec...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-03-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/63512 |
| _version_ | 1811200022551724032 |
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| author | Emily Hsu Nathan R Zemke Arnold J Berk |
| author_facet | Emily Hsu Nathan R Zemke Arnold J Berk |
| author_sort | Emily Hsu |
| collection | DOAJ |
| description | 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, dependent on promoter H3K18/27 acetylation by CBP/p300. We also establish that this is a general transcriptional regulatory mechanism that applies to ~7% 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 the 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. |
| first_indexed | 2024-04-12T01:56:50Z |
| format | Article |
| id | doaj.art-3b7ab3a331a741e2a3d39d4b70dd79c1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:56:50Z |
| publishDate | 2021-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3b7ab3a331a741e2a3d39d4b70dd79c12022-12-22T03:52:46ZengeLife Sciences Publications LtdeLife2050-084X2021-03-011010.7554/eLife.63512Promoter-specific changes in initiation, elongation, and homeostasis of histone H3 acetylation during CBP/p300 inhibitionEmily Hsu0https://orcid.org/0000-0001-5096-0745Nathan R Zemke1https://orcid.org/0000-0002-6326-5925Arnold J Berk2https://orcid.org/0000-0001-9379-6287Molecular Biology Institute, UCLA, Los Angeles, United StatesMolecular Biology Institute, UCLA, Los Angeles, United StatesMolecular Biology Institute, UCLA, Los Angeles, United States; Department of Microbiology, UCLA, Los Angeles, United StatesRegulation 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, dependent on promoter H3K18/27 acetylation by CBP/p300. We also establish that this is a general transcriptional regulatory mechanism that applies to ~7% 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 the 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.https://elifesciences.org/articles/63512adenoviruschromatintranscription |
| spellingShingle | Emily Hsu Nathan R Zemke Arnold J Berk Promoter-specific changes in initiation, elongation, and homeostasis of histone H3 acetylation during CBP/p300 inhibition eLife adenovirus chromatin transcription |
| title | Promoter-specific changes in initiation, elongation, and homeostasis of histone H3 acetylation during CBP/p300 inhibition |
| title_full | Promoter-specific changes in initiation, elongation, and homeostasis of histone H3 acetylation during CBP/p300 inhibition |
| title_fullStr | Promoter-specific changes in initiation, elongation, and homeostasis of histone H3 acetylation during CBP/p300 inhibition |
| title_full_unstemmed | Promoter-specific changes in initiation, elongation, and homeostasis of histone H3 acetylation during CBP/p300 inhibition |
| title_short | Promoter-specific changes in initiation, elongation, and homeostasis of histone H3 acetylation during CBP/p300 inhibition |
| title_sort | promoter specific changes in initiation elongation and homeostasis of histone h3 acetylation during cbp p300 inhibition |
| topic | adenovirus chromatin transcription |
| url | https://elifesciences.org/articles/63512 |
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