MBD4 loss results in global reactivation of promoters and retroelements with low methylated CpG density.

ABSTRACT:

Background

Inherited defects in the base-excision repair gene MBD4 predispose individuals to adenomatous polyposis and colorectal cancer, which is characterized by an accumulation of C > T transitions resulting from spontaneous deamination of 5'-methylcytosine.

Methods

Here, we have investigated the potential role of MBD4 in regulating DNA methylation levels using genome-wide transcriptome and methylome analyses. Additionally, we have elucidated its function through a series of in vitro experiments.

Results

Here we show that the protein MBD4 is required for DNA methylation maintenance and G/T mismatch repair. Transcriptome and methylome analyses reveal a genome-wide hypomethylation of promoters, gene bodies and repetitive elements in the absence of MBD4 in vivo. Methy

SUBMITTER: Papin C 

PROVIDER: S-EPMC10644448 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature