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Cell Rep. 2019 Jun 25;27(13):3770-3779.e7. doi: 10.1016/j.celrep.2019.05.099.

A Role for FACT in RNA Polymerase II Promoter-Proximal Pausing.

Author information

1
Stowers Institute for Medical Research, 1000 E 50th St, Kansas City, MO 64110, USA; The Open University, Walton Hall, Milton Keynes, Buckinghamshire MK7 6AA, UK.
2
Stowers Institute for Medical Research, 1000 E 50th St, Kansas City, MO 64110, USA.
3
Wadsworth Center, New York State Department of Health, PO Box 509, Albany, NY 12201, USA.
4
Stowers Institute for Medical Research, 1000 E 50th St, Kansas City, MO 64110, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
5
Stowers Institute for Medical Research, 1000 E 50th St, Kansas City, MO 64110, USA; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
6
Stowers Institute for Medical Research, 1000 E 50th St, Kansas City, MO 64110, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA. Electronic address: jlc@stowers.org.

Abstract

FACT (facilitates chromatin transcription) is an evolutionarily conserved histone chaperone that was initially identified as an activity capable of promoting RNA polymerase II (Pol II) transcription through nucleosomes in vitro. In this report, we describe a global analysis of FACT function in Pol II transcription in Drosophila. We present evidence that loss of FACT has a dramatic impact on Pol II elongation-coupled processes including histone H3 lysine 4 (H3K4) and H3K36 methylation, consistent with a role for FACT in coordinating histone modification and chromatin architecture during Pol II transcription. Importantly, we identify a role for FACT in the maintenance of promoter-proximal Pol II pausing, a key step in transcription activation in higher eukaryotes. These findings bring to light a broader role for FACT in the regulation of Pol II transcription.

KEYWORDS:

ChIP-nexus; ChIP-seq; FACT; H2A.v; H3K36me3; H3K4me3; PRO-seq; RNA polymerase II; RNA-seq; SSRP1; Spt16; chromatin; promoter-proximal pausing

PMID:
31242411
DOI:
10.1016/j.celrep.2019.05.099
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