Integrative analysis reveals histone demethylase LSD1 promotes RNA polymerase II pausing

Hani Jieun Kim; Pishun Li; Taiyun Kim; Andrew J. Oldfield; Xiaofeng Zheng; Pengyi Yang

iScience (Oct 2022)

Integrative analysis reveals histone demethylase LSD1 promotes RNA polymerase II pausing

Hani Jieun Kim,
Pishun Li,
Taiyun Kim,
Andrew J. Oldfield,
Xiaofeng Zheng,
Pengyi Yang

Affiliations

Hani Jieun Kim: Computational Systems Biology Group, Children’s Medical Research Institute, Westmead, NSW 2145, Australia; School of Mathematics and Statistics, University of Sydney, Sydney, NSW 2006, Australia
Pishun Li: College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China
Taiyun Kim: Computational Systems Biology Group, Children’s Medical Research Institute, Westmead, NSW 2145, Australia; School of Mathematics and Statistics, University of Sydney, Sydney, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, Australia
Andrew J. Oldfield: Institut de Génétique Humaine, Université de Montpellier, CNRS-UMR9002, 34000, Montpellier, France
Xiaofeng Zheng: College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China; Corresponding author
Pengyi Yang: Computational Systems Biology Group, Children’s Medical Research Institute, Westmead, NSW 2145, Australia; School of Mathematics and Statistics, University of Sydney, Sydney, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, Australia; Corresponding author

Journal volume & issue: Vol. 25, no. 10
p. 105049

Abstract

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Summary: Lysine-specific demethylase 1 (LSD1) is well-known for its role in decommissioning enhancers during mouse embryonic stem cell (ESC) differentiation. Its role in gene promoters remains poorly understood despite its widespread presence at these sites. Here, we report that LSD1 promotes RNA polymerase II (RNAPII) pausing, a rate-limiting step in transcription regulation, in ESCs. We found the knockdown of LSD1 preferentially affects genes with higher RNAPII pausing. Next, we demonstrate that the co-localization sites of LSD1 and MYC, a factor known to regulate pause-release, are enriched for other RNAPII pausing factors. We show that LSD1 and MYC directly interact and MYC recruitment to genes co-regulated with LSD1 is dependent on LSD1 but not vice versa. The co-regulated gene set is significantly enriched for housekeeping processes and depleted of transcription factors compared to those bound by LSD1 alone. Collectively, our integrative analysis reveals a pleiotropic role of LSD1 in promoting RNAPII pausing.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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