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. Cardiac anomalies are present in a subset of the cases. H3K23 acylation is also impaired by cancer-derived somatic BRPF1 mutations. Valproate, vorinostat, propionate and butyrate promote H3K23 acylation. These results reveal the dual functionality of BRPF1-KAT6 complexes, shed light on mechanisms underlying related developmental disorders and various cancers, and suggest mutation-based therapy for medical conditions with deficient histone acylation.

A retrospective cohort study, using the electronic medical records of Kaiser Permanente Northern California (2011)(2012)(2013)(2014)(2015), included 560 robotic and 6785 conventional laparoscopic cases with 1836 "complex" patients (25%). The average operative time was 152 minutes (robotic) vs 157 minutes (conventional) laparoscopic hysterectomy. Complex surgical cases averaged 190 minutes and noncomplex cases averaged 144 minutes. For women with complex disease, the robotic approach, when used by a higher-volume surgeon, may be associated with shorter operative time and slightly less blood loss, but not with lower risk of complications.