title: Female bias in Rhox6 and 9 regulation by the histone demethylase KDM6A.
abstract: 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.
authors: Department of Pathology, School of Medicine, University of Washington, Seattle, Washington, United States of America.
authors: Joel B
authors: JB
authors: Berletch
authors: Xinxian
authors: X
authors: Deng
authors: Di Kim
authors: DK
authors: Nguyen
authors: Christine M
authors: CM
authors: Disteche
mesh_terms: D000818:Animals; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D056466:Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics; D051379:Mice; D012098:Reproduction / Q000235:genetics* / Q000502:physiology; D012727:Sex Characteristics; D049951:X Chromosome Inactivation / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; C572371:Rhox6 protein, mouse; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C111778:Utx protein, mouse; C523761:Kdm6b protein, mouse
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