Transcriptional regulation of FACT involves Coordination of chromatin accessibility and CTCF binding

Peijun Wang; Na Fan; Wanting Yang; Pengbo Cao; Guojun Liu; Qi Zhao; Pengfei Guo; Xihe Li; Xinhua Lin; Ning Jiang; Buhe Nashun

doi:10.1016/j.jbc.2023.105538

Transcriptional regulation of FACT involves Coordination of chromatin accessibility and CTCF binding

J Biol Chem. 2024 Jan;300(1):105538. doi: 10.1016/j.jbc.2023.105538. Epub 2023 Dec 10.

Authors

Peijun Wang¹, Na Fan², Wanting Yang³, Pengbo Cao³, Guojun Liu⁴, Qi Zhao⁵, Pengfei Guo⁵, Xihe Li⁶, Xinhua Lin⁷, Ning Jiang⁸, Buhe Nashun⁹

Affiliations

¹ Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, Inner Mongolia University, Hohhot, China; State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China; School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, China.
² Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, Inner Mongolia University, Hohhot, China; State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China.
³ Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, Inner Mongolia University, Hohhot, China.
⁴ School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, China.
⁵ Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, Inner Mongolia University, Hohhot, China; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
⁶ Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, Inner Mongolia University, Hohhot, China; Inner Mongolia Saikexing Institute of Breeding and Reproductive Biotechnology in Domestic Animals, Hohhot, China.
⁷ State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
⁸ State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China. Electronic address: ningjiang@fudan.edu.cn.
⁹ Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, Inner Mongolia University, Hohhot, China; State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China. Electronic address: bnashun@imu.edu.cn.

Abstract

Histone chaperone FACT (facilitates chromatin transcription) is well known to promote chromatin recovery during transcription. However, the mechanism how FACT regulates genome-wide chromatin accessibility and transcription factor binding has not been fully elucidated. Through loss-of-function studies, we show here that FACT component Ssrp1 is required for DNA replication and DNA damage repair and is also essential for progression of cell phase transition and cell proliferation in mouse embryonic fibroblast cells. On the molecular level, absence of the Ssrp1 leads to increased chromatin accessibility, enhanced CTCF binding, and a remarkable change in dynamic range of gene expression. Our study thus unequivocally uncovers a unique mechanism by which FACT complex regulates transcription by coordinating genome-wide chromatin accessibility and CTCF binding.

Keywords: CTCF; FACT; Ssrp1; chromatin accessibility; histone chaperone; transcription.

MeSH terms

Animals
CCCTC-Binding Factor* / genetics
CCCTC-Binding Factor* / metabolism
Chromatin* / genetics
DNA Repair
DNA Replication
DNA-Binding Proteins* / genetics
Gene Expression Regulation*
High Mobility Group Proteins* / genetics
Histone Chaperones* / genetics
Mice
NIH 3T3 Cells

Substances

CCCTC-Binding Factor
Chromatin
Histone Chaperones
Ssrp1 protein, mouse
DNA-Binding Proteins
High Mobility Group Proteins