RNA Pol II Dynamics Modulate Co-transcriptional Chromatin Modification, CTD Phosphorylation, and Transcriptional Direction

Molecular Cell
Nova FongDavid L Bentley

Abstract

Eukaryotic genes are marked by conserved post-translational modifications on the RNA pol II C-terminal domain (CTD) and the chromatin template. How the 5'-3' profiles of these marks are established is poorly understood. Using pol II mutants in human cells, we found that slow transcription repositioned specific co-transcriptionally deposited chromatin modifications; histone H3 lysine 36 trimethyl (H3K36me3) shifted within genes toward 5' ends, and histone H3 lysine 4 dimethyl (H3K4me2) extended farther upstream of start sites. Slow transcription also evoked a hyperphosphorylation of CTD Ser2 residues at 5' ends of genes that is conserved in yeast. We propose a "dwell time in the target zone" model to explain the effects of transcriptional dynamics on the establishment of co-transcriptionally deposited protein modifications. Promoter-proximal Ser2 phosphorylation is associated with a longer pol II dwell time at start sites and reduced transcriptional polarity because of strongly enhanced divergent antisense transcription at promoters. These results demonstrate that pol II dynamics help govern the decision between sense and divergent antisense transcription.

Citations

Aug 29, 2018·Genes & Development·Benjamin EricksonDavid L Bentley
Mar 9, 2019·Genes & Development·Yoo Jin JooStephen Buratowski
Nov 17, 2019·Genome Research·Yuko Hasegawa, Kevin Struhl
Dec 7, 2019·The Journal of Biological Chemistry·H Karimi KinyamuTrevor K Archer
Feb 28, 2020·EMBO Reports·Xueyuan LengSebastian Marquardt
Jul 6, 2019·PloS One·Adam P TellierJesse Mager
May 14, 2020·Transcription·Danielle E LyonsMelanie Ott
Dec 1, 2019·Scientific Reports·Irina HeckmannStefan Jentsch
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