Title: A DNMT3A2-HDAC2 Complex Is Essential for Genomic Imprinting and Genome Integrity in Mouse Oocytes.
Authors: Ma, Pengpeng; de Waal, Eric; Weaver, Jamie R; Bartolomei, Marisa S; Schultz, Richard M
Published In Cell Rep, (2015 Nov 24)
Abstract: Maternal genomic imprints are established during oogenesis. Histone deacetylases (HDACs) 1 and 2 are required for oocyte development in mouse, but their role in genomic imprinting is unknown. We find that Hdac1:Hdac2(-/-) double-mutant growing oocytes exhibit global DNA hypomethylation and fail to establish imprinting marks for Igf2r, Peg3, and Srnpn. Global hypomethylation correlates with increased retrotransposon expression and double-strand DNA breaks. Nuclear-associated DNMT3A2 is reduced in double-mutant oocytes, and injecting these oocytes with Hdac2 partially restores DNMT3A2 nuclear staining. DNMT3A2 co-immunoprecipitates with HDAC2 in mouse embryonic stem cells. Partial loss of nuclear DNMT3A2 and HDAC2 occurs in Sin3a(-/-) oocytes, which exhibit decreased DNA methylation of imprinting control regions for Igf2r and Srnpn, but not Peg3. These results suggest seminal roles of HDAC1/2 in establishing maternal genomic imprints and maintaining genomic integrity in oocytes mediated in part through a SIN3A complex that interacts with DNMT3A2.
PubMed ID: 26586441
MeSH Terms: Animals; DNA (Cytosine-5-)-Methyltransferases/genetics*; DNA Breaks, Double-Stranded; DNA Methylation/genetics; Embryonic Stem Cells/physiology; Gene Expression Regulation, Developmental/genetics; Genome/genetics*; Genomic Imprinting/genetics*; Histone Deacetylase 1/genetics; Histone Deacetylase 2/genetics*; Mice; Oocytes/physiology*; Oogenesis/genetics; Repressor Proteins/genetics