Effects of histone acetyltransferase dead mutation of KAT6A and KAT6B on gene expression in E9.5 mouse embryos and E14.5 mouse foetal liver hematopoietic cells

The paralogous histone acetyltransferases KAT6A and KAT6B are large 200 kDa proteins of identical protein domain structure with high sequence similarity within the functional protein domains. Kat6a and Kat6b null mutation have severe effects on mouse embryonic and foetal development as well as on adult stem cell populations. Apart from the well-defined MYST family histone acetyltransferase domain, the proteins have N-terminal winged-helix domains followed by tandem plant homeodomain fingers preceding the histone acetyltransferase domain, as well as a long unstructured acidic region and serine and methionine rich regions following the histone acetyltransferase domain. In this study we examined the effects of point mutations that reduce the histone acetyltransferase function to background levels on gene expression in E9.5 mouse embryos and E14.5 mouse foetal liver haematopoietic cells and compared these to the effects of the null mutations of the Kat6a and Kat6b gene.