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| Status |
Public on Jul 11, 2017 |
| Title |
Acetylation on Histone H3 Lysine 9 Mediates a Switch from Transcription Initiation to Elongation |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The transition from transcription initiation to elongation is a key regulatory step in gene expression, which requires RNA polymerase II (Pol II) to escape promoter proximal pausing on chromatin. While elongation factors promote pause release leading to transcription elongation, the role of epigenetic modifications during this critical transition step is poorly understood. Two histone marks on histone H3, lysine 4 trimethylation (H3K4me3) and lysine 9 acetylation (H3K9ac), co-localize on active gene promoters and are associated with active transcription. H3K4me3 can promote transcription initiation, yet the functional role of H3K9ac is much less understood. We hypothesized that H3K9ac may function downstream of transcription initiation by recruiting specific proteins important for the next step of transcription. Here, we describe a functional role for H3K9ac in promoting Pol II pause release by directly recruiting the super elongation complex (SEC) to chromatin. H3K9ac serves as a substrate for direct binding of the SEC, as does acetylation of histone H4 lysine 5 (H4K5ac), to a lesser extent. Furthermore, lysine 9 on histone H3 is necessary for maximal Pol II pause release through SEC action, and loss of H3K9ac increases the Pol II pausing index on a subset of genes in HeLa cells. At select gene promoters, loss of H3K9ac or depletion of the SEC reduces gene expression and increases paused Pol II occupancy. We therefore propose that an ordered histone code drives progression through the transcription cycle, providing new mechanistic insight that SEC recruitment to certain acetylated histones promotes the subsequent release of paused Pol II needed for transcription elongation.
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| |
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| Overall design |
ChIP-seq analysis of Pol II in HeLa cells transfected with non-targeting control siRNAs or siRNAs targeting GCN5 (KAT2A) and PCAF (KAT2B) in duplicate
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| |
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| Contributor(s) |
O'Malley BW, Li W, Foulds CE |
| Citation(s) |
28717009 |
| |
| Submission date |
Jun 13, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Jiejun Shi |
| E-mail(s) |
jiejuns@uci.edu
|
| Organization name |
University of California Irvine
|
| Department |
School of Medicine
|
| Lab |
Li lab
|
| Street address |
5270 California Ave
|
| City |
Irvine |
| State/province |
CA |
| ZIP/Postal code |
92617 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (5)
|
| GSM2667594 |
Pol II ChIP-seq siRNA control replicate 1 |
| GSM2667595 |
Pol II ChIP-seq siRNA control replicate 2 |
| GSM2667596 |
Pol II ChIP-seq siKAT2A/B replicate 1 |
|
| Relations |
| BioProject |
PRJNA390303 |
| SRA |
SRP109117 |
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