Kristjan H Gretarsson, Stephen Abini-Agbomson, Susan L Gloor, Daniel N Weinberg, Jamie L McCuiston, Vishnu Udayakumar Sunitha Kumary, Allison R Hickman, Varun Sahu, Rachel Lee, Xinjing Xu, Natalie Lipieta, Samuel Flashner, Oluwatobi A Adeleke, Irina K Popova, Hailey F Taylor, Kelsey Noll, Carolina Lin Windham, Danielle N Maryanski, Bryan J Venters, Hiroshi Nakagawa, Michael-Christopher Keogh, Karim-Jean Armache, Chao Lu
During tumor development, promoter CpG islands (CGIs) that are normally silenced by Polycomb repressive complexes (PRCs) become DNA hypermethylated. The molecular mechanism by which de novo DNA methyltransferase(s) catalyze CpG methylation at PRC-regulated regions remains unclear. Here we report a cryo-EM structure of the DNMT3A long isoform (DNMT3A1) N-terminal region in complex with a nucleosome carrying PRC1-mediated histone H2A lysine 119 monoubiquitination (H2AK119Ub). We identify regions within the DNMT3A1 N-terminus that bind H2AK119Ub and the nucleosome acidic patch...
March 20, 2024: bioRxiv