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UHRF1 is a mediator of KRAS driven oncogenesis in lung adenocarcinoma [epic_methyl]

ABSTRACT: Methylation array was performed to understand the role of UHRF1 in DNA methylation in KRAS mutant lung cancer cell lines. Knock-down of UHRF1 leads to significant changes in global DNA methylation in both cell lines.

ORGANISM(S): Homo sapiens

PROVIDER: GSE198446 | GEO | 2023/05/15

REPOSITORIES: GEO

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UHRF1 is a mediator of KRAS driven oncogenesis in lung adenocarcinoma [RNA-seq]

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UHRF1 is a mediator of KRAS driven oncogenesis in lung adenocarcinoma [CRISPR_screen]

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UHRF1 is a mediator of KRAS driven oncogenesis in lung adenocarcinoma [shRNA]

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UHRF1 is a mediator of KRAS driven oncogenesis in lung adenocarcinoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-05-15 | GSE198450 | GEO

Identificaiton of novel acetylation sites in UHRF1 mediated by acetyltransferase MOF

Project description:The multi-domain protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) recruits DNMT1 for DNA methylation maintenance during DNA replication. Here, we show that MOF (Males absent On the First) is an acetyltransferase of UHRF1 to acetylate UHRF1 at Lys670 in the pre-RING linker region whereas HDAC1 is a deacetylase of UHRF1 at the same site. The MOF/HDAC1-mediated acetylation in UHRF1 is cell-cycle regulated and peaks at G1/S phase, in line with the function of UHRF1 in recruiting DNMT1 to maintain DNA methylation. In addition, UHRF1 acetylation significantly enhances its E3 ligase activity and elimination of UHRF1 acetylation at these sites attenuates UHRF1-mediated H3 ubiquitination, which in turn impairs the DNMT1 recruitment and DNA methylation. Taken together, these findings not only identify MOF as a new acetyltransferase for UHRF1 but also reveal a novel mechanism underlying the regulation of DNA methylation maintenance through MOF-mediated UHRF1 acetylation.

2024-03-06 | PXD040426 | Pride

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