Rabbit anti-Mouse Histone acetyltransferase MYST3 polyclonal antibody

Neurodevelopmental disorders (NDD) are common, with 1-3% of general population being affected, but the etiology is unknown in most individuals. Clinical whole-exome sequencing (WES) has proven to be a powerful tool for the identification of pathogenic variants leading to Mendelian disorders, among which NDD represent a significant percentage. Performing WES with a trio-approach has proven to be extremely effective in identifying de novo pathogenic variants as a common cause of NDD. Here we report six unrelated individuals with a common phenotype consisting of NDD with severe speech delay, hypotonia, and facial dysmorphism. These patients underwent WES with a trio approach and de novo heterozygous predicted pathogenic novel variants in the KAT6A gene were identified. The KAT6A gene encodes a histone acetyltransfrease protein and it has long been known for its structural involvement in acute myeloid leukemia; however, it has not previously been associated with any congenital disorder. In animal models the KAT6A ortholog is involved in transcriptional regulation during development. Given the similar findings in animal models and our patient's phenotypes, we hypothesize that KAT6A could play a role in development of the brain, face, and heart in humans. (C) 2016 Wiley Periodicals, Inc.

We report that embryos deficient in the histone acetyltransferase Moz (Myst3/Kat6a) show histone H3 lysine 9 (H3K9) hypoacetylation, corresponding H3K9 hypermethylation, and reduced transcription at Hox gene loci. Consistent with an observed caudal shift in Hox gene expression, segment identity is shifted anteriorly, such that Moz-deficient mice show a profound homeotic transformation of the axial skeleton and the nervous system. Intriguingly, histone acetylation defects are relatively specific to H3K9 at Hox loci, as neither Hox H3K14 acetylation nor bulk H3K9 acetylation levels throughout the genome are strongly affected; H4K16 acetylation actually increases in the absence of Moz. H3K9 hypoacetylation, Hox gene repression, and the homeotic transformation caused by lack of Moz are all reversed by treatment with retinoic acid (RA). In conclusion, our data show that Moz regulates H3K9 acetylation at Hox gene loci and that RA can act independently of Moz to establish specific Hox gene expression boundaries.