Female bias in Rhox6 and 9 regulation by the histone demethylase KDM6A.

The Rhox cluster on the mouse X chromosome contains reproduction-related homeobox genes expressed in a sexually dimorphic manner. We report that two members of the Rhox cluster, Rhox6 and 9, are regulated by de-methylation of histone H3 at lysine 27 by KDM6A, a histone demethylase with female-biased...

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Main Authors: Joel B Berletch, Xinxian Deng, Di Kim Nguyen, Christine M Disteche
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-05-01
Series:PLoS Genetics
Online Access:http://europepmc.org/articles/PMC3642083?pdf=render
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author Joel B Berletch
Xinxian Deng
Di Kim Nguyen
Christine M Disteche
author_facet Joel B Berletch
Xinxian Deng
Di Kim Nguyen
Christine M Disteche
author_sort Joel B Berletch
collection DOAJ
description The Rhox cluster on the mouse X chromosome contains reproduction-related homeobox genes expressed in a sexually dimorphic manner. We report that two members of the Rhox cluster, Rhox6 and 9, are regulated by de-methylation of histone H3 at lysine 27 by KDM6A, a histone demethylase with female-biased expression. Consistent with other homeobox genes, Rhox6 and 9 are in bivalent domains prior to embryonic stem cell differentiation and thus poised for activation. In female mouse ES cells, KDM6A is specifically recruited to Rhox6 and 9 for gene activation, a process inhibited by Kdm6a knockdown in a dose-dependent manner. In contrast, KDM6A occupancy at Rhox6 and 9 is low in male ES cells and knockdown has no effect on expression. In mouse ovary where Rhox6 and 9 remain highly expressed, KDM6A occupancy strongly correlates with expression. Our study implicates Kdm6a, a gene that escapes X inactivation, in the regulation of genes important in reproduction, suggesting that KDM6A may play a role in the etiology of developmental and reproduction-related effects of X chromosome anomalies.
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spelling doaj.art-714924d8ee8c4257aa365af23b2d20602022-12-21T20:04:33ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-05-0195e100348910.1371/journal.pgen.1003489Female bias in Rhox6 and 9 regulation by the histone demethylase KDM6A.Joel B BerletchXinxian DengDi Kim NguyenChristine M DistecheThe Rhox cluster on the mouse X chromosome contains reproduction-related homeobox genes expressed in a sexually dimorphic manner. We report that two members of the Rhox cluster, Rhox6 and 9, are regulated by de-methylation of histone H3 at lysine 27 by KDM6A, a histone demethylase with female-biased expression. Consistent with other homeobox genes, Rhox6 and 9 are in bivalent domains prior to embryonic stem cell differentiation and thus poised for activation. In female mouse ES cells, KDM6A is specifically recruited to Rhox6 and 9 for gene activation, a process inhibited by Kdm6a knockdown in a dose-dependent manner. In contrast, KDM6A occupancy at Rhox6 and 9 is low in male ES cells and knockdown has no effect on expression. In mouse ovary where Rhox6 and 9 remain highly expressed, KDM6A occupancy strongly correlates with expression. Our study implicates Kdm6a, a gene that escapes X inactivation, in the regulation of genes important in reproduction, suggesting that KDM6A may play a role in the etiology of developmental and reproduction-related effects of X chromosome anomalies.http://europepmc.org/articles/PMC3642083?pdf=render
spellingShingle Joel B Berletch
Xinxian Deng
Di Kim Nguyen
Christine M Disteche
Female bias in Rhox6 and 9 regulation by the histone demethylase KDM6A.
PLoS Genetics
title Female bias in Rhox6 and 9 regulation by the histone demethylase KDM6A.
title_full Female bias in Rhox6 and 9 regulation by the histone demethylase KDM6A.
title_fullStr Female bias in Rhox6 and 9 regulation by the histone demethylase KDM6A.
title_full_unstemmed Female bias in Rhox6 and 9 regulation by the histone demethylase KDM6A.
title_short Female bias in Rhox6 and 9 regulation by the histone demethylase KDM6A.
title_sort female bias in rhox6 and 9 regulation by the histone demethylase kdm6a
url http://europepmc.org/articles/PMC3642083?pdf=render
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AT dikimnguyen femalebiasinrhox6and9regulationbythehistonedemethylasekdm6a
AT christinemdisteche femalebiasinrhox6and9regulationbythehistonedemethylasekdm6a