Pluripotency State Transition of Embryonic Stem Cells Requires the Turnover of Histone Chaperone FACT on Chromatin

Overview

Journal iScience

Publisher Cell Press

Date 2024 Jan 12

PMID 38213626

Authors

Hang Zhao

Di Li

Xue Xiao

Cuifang Liu

Guifang Chen

Xiaoyu Su

Zhenxin Yan

Shijia Gu

Yizhou Wang

Guohong Li

Jianxun Feng

Wei Li

Ping Chen

Jiayi Yang

Qing Li

Affiliations

Soon will be listed here.

Abstract

The differentiation of embryonic stem cells (ESCs) begins with the transition from the naive to the primed state. The formative state was recently established as a critical intermediate between the two states. Here, we demonstrate the role of the histone chaperone FACT in regulating the naive-to-formative transition. We found that the Q265K mutation in the FACT subunit SSRP1 increased the binding of FACT to histone H3-H4, impaired nucleosome disassembly , and reduced the turnover of FACT on chromatin . Strikingly, mouse ESCs harboring this mutation showed elevated naive-to-formative transition. Mechanistically, the SSRP1-Q265K mutation enriched FACT at the enhancers of formative-specific genes to increase targeted gene expression. Together, these findings suggest that the turnover of FACT on chromatin is crucial for regulating the enhancers of formative-specific genes, thereby mediating the naive-to-formative transition. This study highlights the significance of FACT in fine-tuning cell fate transition during early development.

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