UC Riverside

Mammalian DNA methylation serves an important role in epigenetic regulation. The methylation marks are imprinted by de novo methyltransferases DNMT3A and DNMT3B during gametogenesis and early embryonic development, and further preserved by UHRF1-mediated maintenance DNA methylation machinery in each cell cycle. Here, we present the crystal structures of an intramolecular complex UHRF1, as well as DNMT3B-DNMT3L tetramer in complex with CpG/CpA DNA, respectively. Combined with biochemical and functional analysis, we’ve revealed the molecular basis of the allosteric regulation of UHRF1 and DNMT3B-mediated de novo DNA methylation, which comprehensively provides mechanistic insights in mammalian DNA methylation.