Kezhi Yan, Justine Rousseau, Keren Machol, Laura A Cross, Katherine E Agre, Cynthia Forster Gibson, Anne Goverde, Kendra L Engleman, Hannah Verdin, Elfride De Baere, Lorraine Potocki, Dihong Zhou, Maxime Cadieux-Dion, Gary A Bellus, Monisa D Wagner, Rebecca J Hale, Natacha Esber, Alan F Riley, Benjamin D Solomon, Megan T Cho, Kirsty McWalter, Roy Eyal, Meagan K Hainlen, Bryce A Mendelsohn, Hillary M Porter, Brendan C Lanpher, Andrea M Lewis, Juliann Savatt, Isabelle Thiffault, Bert Callewaert, Philippe M Campeau, Xiang-Jiao Yang
Lysine acetyltransferase 6A (KAT6A) and its paralog KAT6B form stoichiometric complexes with bromodomain- and PHD finger-containing protein 1 (BRPF1) for acetylation of histone H3 at lysine 23 (H3K23). We report that these complexes also catalyze H3K23 propionylation in vitro and in vivo. Immunofluorescence microscopy and ATAC-See revealed the association of this modification with active chromatin. Brpf1 deletion obliterates the acylation in mouse embryos and fibroblasts. Moreover, we identify BRPF1 variants in 12 previously unidentified cases of syndromic intellectual disability and demonstrate that these cases and known BRPF1 variants impair H3K23 propionylation...
January 2020: Science Advances