title: Moz and retinoic acid coordinately regulate H3K9 acetylation, Hox gene expression, and segment identity.
abstract: 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.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. avoss@wehi.edu.au
authors.forename: Anne K
authors.initials: AK
authors.lastname: Voss
authors.forename: Caitlin
authors.initials: C
authors.lastname: Collin
authors.forename: Mathew P
authors.initials: MP
authors.lastname: Dixon
authors.forename: Tim
authors.initials: T
authors.lastname: Thomas
mesh_terms: D000107:Acetylation; D000818:Animals; D015415:Biomarkers; D004622:Embryo, Mammalian / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D006657:Histones; D014212:Tretinoin; D051548:Histone Acetyltransferases; C511438:MOZ protein, mouse; D008239:Lysine