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MOZ Regulates the Tbx1 Locus, and Moz Mutation Partially Phenocopies DiGeorge Syndrome
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 modificatio...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442180/ https://www.ncbi.nlm.nih.gov/pubmed/22921202 http://dx.doi.org/10.1016/j.devcel.2012.07.010 |
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author | Voss, Anne K. Vanyai, Hannah K. Collin, Caitlin Dixon, Mathew P. McLennan, Tamara J. Sheikh, Bilal N. Scambler, Peter Thomas, Tim |
author_facet | Voss, Anne K. Vanyai, Hannah K. Collin, Caitlin Dixon, Mathew P. McLennan, Tamara J. Sheikh, Bilal N. Scambler, Peter Thomas, Tim |
author_sort | Voss, Anne K. |
collection | PubMed |
description | 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 with Tbx1 haploinsufficiency or oversupply of retinoic acid. Conversely, a Tbx1 transgene rescues the heart phenotype in Moz mutants. Our data reveal a molecular mechanism for a specific chromatin modification of the Tbx1 locus intersecting with an environmental determinant, modeling variability in DiGeorge syndrome. |
format | Online Article Text |
id | pubmed-3442180 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-34421802012-09-26 MOZ Regulates the Tbx1 Locus, and Moz Mutation Partially Phenocopies DiGeorge Syndrome Voss, Anne K. Vanyai, Hannah K. Collin, Caitlin Dixon, Mathew P. McLennan, Tamara J. Sheikh, Bilal N. Scambler, Peter Thomas, Tim Dev Cell Article 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 with Tbx1 haploinsufficiency or oversupply of retinoic acid. Conversely, a Tbx1 transgene rescues the heart phenotype in Moz mutants. Our data reveal a molecular mechanism for a specific chromatin modification of the Tbx1 locus intersecting with an environmental determinant, modeling variability in DiGeorge syndrome. Cell Press 2012-09-11 /pmc/articles/PMC3442180/ /pubmed/22921202 http://dx.doi.org/10.1016/j.devcel.2012.07.010 Text en © 2012 ELL & Excerpta Medica. https://creativecommons.org/licenses/by-nc-nd/3.0/ Open Access under CC BY-NC-ND 3.0 (https://creativecommons.org/licenses/by-nc-nd/3.0/) license |
spellingShingle | Article Voss, Anne K. Vanyai, Hannah K. Collin, Caitlin Dixon, Mathew P. McLennan, Tamara J. Sheikh, Bilal N. Scambler, Peter Thomas, Tim MOZ Regulates the Tbx1 Locus, and Moz Mutation Partially Phenocopies DiGeorge Syndrome |
title | MOZ Regulates the Tbx1 Locus, and Moz Mutation Partially Phenocopies DiGeorge Syndrome |
title_full | MOZ Regulates the Tbx1 Locus, and Moz Mutation Partially Phenocopies DiGeorge Syndrome |
title_fullStr | MOZ Regulates the Tbx1 Locus, and Moz Mutation Partially Phenocopies DiGeorge Syndrome |
title_full_unstemmed | MOZ Regulates the Tbx1 Locus, and Moz Mutation Partially Phenocopies DiGeorge Syndrome |
title_short | MOZ Regulates the Tbx1 Locus, and Moz Mutation Partially Phenocopies DiGeorge Syndrome |
title_sort | moz regulates the tbx1 locus, and moz mutation partially phenocopies digeorge syndrome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442180/ https://www.ncbi.nlm.nih.gov/pubmed/22921202 http://dx.doi.org/10.1016/j.devcel.2012.07.010 |
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