Chromatin Assembly Factor 1 (CAF-1) facilitates the establishment of facultative heterochromatin during pluripotency exit

Liang Cheng, Xu Zhang, Yan Wang, Haiyun Gan, Xiaowei Xu, Xiangdong Lv, Xu Hua, Jianwen Que, Tamas Ordog, Zhiguo Zhang

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Establishment and subsequent maintenance of distinct chromatin domains during embryonic stem cell (ESC) differentiation are crucial for lineage specification and cell fate determination. Here we show that the histone chaperone Chromatin Assembly Factor 1 (CAF-1), which is recruited to DNA replication forks through its interaction with proliferating cell nuclear antigen (PCNA) for nucleosome assembly, participates in the establishment of H3K27me3-mediated silencing during differentiation. Deletion of CAF-1 p150 subunit impairs the silencing of many genes including Oct4, Sox2 and Nanog as well as the establishment of H3K27me3 at these gene promoters during ESC differentiation. Mutations of PCNA residues involved in recruiting CAF-1 to the chromatin also result in defects in differentiation in vitro and impair early embryonic development as p150 deletion. Together, these results reveal that the CAF-1-PCNA nucleosome assembly pathway plays an important role in the establishment of H3K27me3-mediated silencing during cell fate determination.

Original languageEnglish (US)
Pages (from-to)11114-11131
Number of pages18
JournalNucleic acids research
Volume47
Issue number21
DOIs
StatePublished - Dec 2 2019

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Chromatin Assembly Factor 1 (CAF-1) facilitates the establishment of facultative heterochromatin during pluripotency exit'. Together they form a unique fingerprint.

Cite this