Methylation of recombinant mononucleosomes by DNMT3A demonstrates efficient linker DNA methylation and a role of H3K36me3.

ABSTRACT: Recently, the structure of the DNMT3A2/3B3 heterotetramer complex bound to a mononucleosome was reported. Here, we investigate DNA methylation of recombinant unmodified, H3K_C4me3 and H3K_C36me3 containing mononucleosomes by DNMT3A2, DNMT3A catalytic domain (DNMT3AC) and the DNMT3AC/3B3C complex. We show strong protection of the nucleosomal bound DNA against methylation, but efficient linker-DNA methylation next to the nucleosome core. High and low methylation levels of two specific CpG sites next to the nucleosome core agree well with details of the DNMT3A2/3B3-nucleosome structure. Linker DNA methylation next to the nucleosome is increased in the absence of H3K4me3, likely caused by binding of the H3-tail to the ADD domain leading to relief of autoinhibition. Our data

SUBMITTER: Brohm A 

PROVIDER: S-EPMC8891314 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature