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Acetylation of UHRF1 Regulates Hemi-methylated DNA Binding and Maintenance of Genome-wide DNA Methylation

Cited 15 time in Web of Science Cited 16 time in Scopus
Authors

Hahm, Ja Young; Park, Jin Woo; Kang, Joo-Young; Park, Junyoung; Kim, Chul-Hong; Kim, Ji-Young; Ha, Nam-Chul; Kim, Jung-Woong; Seo, Sang-Beom

Issue Date
2020-07
Publisher
Cell Press
Citation
Cell Reports, Vol.32 No.4, p. 107958
Abstract
UHRF1 is a key regulator in DNA methylation maintenance. It binds histone H3K9me2/3 and hemi-methylated DNA and recruits DNMT1 to DNA replication forks during S phase. However, the regulatory mechanism of hemi-methylated DNA binding activity of UHRF1 remains unknown. In this study, we reveal that acetylation of UHRF1 is regulated by PCAF and HDAC1. We show that UHRF1 acetylation at K490 attenuates its binding affinity to hemi-methylated DNA. We analyze genome-wide DNA methylation and gene-expression patterns using stable cell lines and discover that cells where the endogenous UHRF1 is replaced with an acetyl-mimetic (UHRF1 K490Q) mutant show deficiencies in inherited DNA methylation and show different gene-expression patterns in genes related to cell survival. These results reveal that precise regulation of UHRF1 acetylation is required to maintain DNA methylation during cell division and control cell survival.
ISSN
2211-1247
URI
https://hdl.handle.net/10371/179914
DOI
https://doi.org/10.1016/j.celrep.2020.107958
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