New publication in "J. Biol. Chem."

New publication in "J. Biol. Chem."

Structural and biochemical studies showed that the DNA methyltransferase DNMT3A/DNMT3B3 (3A/3B3) heterotetramers directly interact with the nucleosomal acidic patch. Here, we investigated linker DNA methylation by DNMT3A/3B3 using dinucleosome substrates with different linker lengths and sequence and demonstrate that the contact to the acid patch improves 3A/3B3 recruitment to nucleosomes and methylation of linker DNA. Characteristic methylation levels of CpG sites next to the nucleosomes suggest that 3A/3B3 complexes are anchored on both sides of the linker DNA to nucleosomes and the DNMT3A complexes multimerize on the linker DNA. This multimerization spatially organizes the complexes, aligning active sites of DNMT3A complexes with CpG sites, which then leads to the observed methylation patterns. Our data suggest that multimerization of DNMT3A on linker DNA could shape the DNA methylation landscape in cells with potential implications on nucleosome positioning particularly in heterochromatic regions.