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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.
Pubmed ID: 32726623
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Software package for Illumina 450 methylation array normalization and metrics including 15 flavors of betas and three performance metrics, with methods for objects produced by methylumi, minfi and IMA packages.
View all literature mentionsCell line K-562 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Ac-lysine (7F8)
View all literature mentionsThis monoclonal targets Histone H3
View all literature mentionsThis monoclonal targets PCAF (E-8)
View all literature mentionsThis monoclonal targets UHRF1 (H-8)
View all literature mentionsThis polyclonal targets acetyl Lysine antibody - ChIP Grade
View all literature mentionsThis monoclonal targets PCNA (PC10)
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis unknown targets Rabbit Normal igg Control antibody
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis polyclonal secondary targets not applicable
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