Journal article
MOZ Regulates the Tbx1 Locus, and Moz Mutation Partially Phenocopies DiGeorge Syndrome
AK Voss, HK Vanyai, C Collin, MP Dixon, TJ McLennan, BN Sheikh, P Scambler, T Thomas
Developmental Cell | CELL PRESS | Published : 2012
Open access
Abstract
DiGeorge syndrome, caused by a 22q11 microdeletion or mutation of the TBX1 gene, varies in severity greatly, even among monozygotic twins. Epigenetic phenomena have been invoked to explain phenotypic differences in individuals of identical genetic composition, although specific chromatin modifications relevant to DiGeorge syndrome are elusive. Here we show that lack of the histone acetyltransferase MOZ (MYST3/KAT6A) phenocopies DiGeorge syndrome, and the MOZ complex occupies the Tbx1 locus, promoting its expression and histone 3 lysine 9 acetylation. Importantly, DiGeorge syndrome-like anomalies are present in mice with homozygous mutation of Moz and in heterozygous Moz mutants when combined..
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Awarded by British Heart Foundation
Funding Acknowledgements
We thank N. Downer, C. Gatt, and L. Sampurno for excellent technical assistance. We gratefully acknowledge A. Baldini for helpful advice on the manuscript and provision of the Tbx1 mutant mice. We thank V.E. Papaiaonnou for supplying T box cDNA probes. This work was supported by the Australian National Health and Medical Research Council (project grants, senior research fellowships to A.K.V. and T.T.; scholarship to B.N.S.), the Australian Stem Cell Centre (program module to A.K.V. and T.T.; scholarship to B.N.S.), the British Heart Foundation (PG/10/032/28333 RG/10/13/28570 to P.S.), and Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.