Loss of KAT6B causes premature ossification and promotes osteoblast differentiation during development

Abstract

The MYST family histone acetyltransferase gene, KAT6B (MYST4, MORF, QKF) is mutated in two distinct human congenital disorders characterised by intellectual disability, facial dysmorphogenesis and skeletal abnormalities; the Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome and Genitopatellar syndrome. Despite its requirement in normal skeletal development, the cellular and transcriptional effects of KAT6B in skeletogenesis have not been thoroughly studied. Here, we show that germline deletion of the Kat6b gene in mice causes premature ossification in vivo, resulting in shortened craniofacial elements and increased bone density, as well as shortened tibias with an expanded pre-hype..