Genomics

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158

Acetylation on Histone H3 Lysine 9 Mediates a Switch from Transcription Initiation to Elongation


ABSTRACT: 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. 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

INSTRUMENT(S): Illumina HiSeq 2000 (Homo sapiens)

SUBMITTER: Jiejun Shi  

PROVIDER: GSE99998 | GEO | 2017-07-11

SECONDARY ACCESSION(S): PRJNA390303

REPOSITORIES: GEO

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Acetylation on histone H3 lysine 9 mediates a switch from transcription initiation to elongation.

Gates Leah A LA   Shi Jiejun J   Rohira Aarti D AD   Feng Qin Q   Zhu Bokai B   Bedford Mark T MT   Sagum Cari A CA   Jung Sung Yun SY   Qin Jun J   Tsai Ming-Jer MJ   Tsai Sophia Y SY   Li Wei W   Foulds Charles E CE   O'Malley Bert W BW  

The Journal of biological chemistry 20170717 35


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. Although 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 acti  ...[more]

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