Distinct roles of androgen receptor, estrogen receptor alpha, and BCL6 in the establishment of sex-biased DNA methylation in mouse liver

Abstract Sexual dimorphism in gene regulation, including DNA methylation, is the main driver of sexual dimorphism in phenotypes. However, the questions of how and when sex shapes DNA methylation remain unresolved. Recently, using mice with different combinations of genetic and phenotypic sex, we ide...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Najla AlOgayil, Klara Bauermeister, Jose Hector Galvez, Varun S. Venkatesh, Qinwei Kim-wee Zhuang, Matthew L. Chang, Rachel A. Davey, Jeffrey D. Zajac, Kinuyo Ida, Akihide Kamiya, Teruko Taketo, Guillaume Bourque, Anna K. Naumova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/01f3318d5de14971bc8fe6b025ea3a3a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:01f3318d5de14971bc8fe6b025ea3a3a
record_format	dspace
spelling	oai:doaj.org-article:01f3318d5de14971bc8fe6b025ea3a3a2021-12-02T16:31:57ZDistinct roles of androgen receptor, estrogen receptor alpha, and BCL6 in the establishment of sex-biased DNA methylation in mouse liver10.1038/s41598-021-93216-62045-2322https://doaj.org/article/01f3318d5de14971bc8fe6b025ea3a3a2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93216-6https://doaj.org/toc/2045-2322Abstract Sexual dimorphism in gene regulation, including DNA methylation, is the main driver of sexual dimorphism in phenotypes. However, the questions of how and when sex shapes DNA methylation remain unresolved. Recently, using mice with different combinations of genetic and phenotypic sex, we identified sex-associated differentially methylated regions (sDMRs) that depended on the sex phenotype. Focusing on a panel of validated sex-phenotype dependent male- and female-biased sDMRs, we tested the developmental dynamics of sex bias in liver methylation and the impacts of mutations in the androgen receptor, estrogen receptor alpha, or the transcriptional repressor Bcl6 gene. True hermaphrodites that carry both unilateral ovaries and contralateral testes were also tested. Our data show that sex bias in methylation either coincides with or follows sex bias in the expression of sDMR-proximal genes, suggesting that sex bias in gene expression may be required for demethylation at certain sDMRs. Global ablation of AR, ESR1, or a liver-specific loss of BCL6, all alter sDMR methylation, whereas presence of both an ovary and a testis delays the establishment of male-type methylation levels in hermaphrodites. Moreover, the Bcl6-LKO shows dissociation between expression and methylation, suggesting a distinct role of BCL6 in demethylation of intragenic sDMRs.Najla AlOgayilKlara BauermeisterJose Hector GalvezVarun S. VenkateshQinwei Kim-wee ZhuangMatthew L. ChangRachel A. DaveyJeffrey D. ZajacKinuyo IdaAkihide KamiyaTeruko TaketoGuillaume BourqueAnna K. NaumovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Najla AlOgayil Klara Bauermeister Jose Hector Galvez Varun S. Venkatesh Qinwei Kim-wee Zhuang Matthew L. Chang Rachel A. Davey Jeffrey D. Zajac Kinuyo Ida Akihide Kamiya Teruko Taketo Guillaume Bourque Anna K. Naumova Distinct roles of androgen receptor, estrogen receptor alpha, and BCL6 in the establishment of sex-biased DNA methylation in mouse liver
description	Abstract Sexual dimorphism in gene regulation, including DNA methylation, is the main driver of sexual dimorphism in phenotypes. However, the questions of how and when sex shapes DNA methylation remain unresolved. Recently, using mice with different combinations of genetic and phenotypic sex, we identified sex-associated differentially methylated regions (sDMRs) that depended on the sex phenotype. Focusing on a panel of validated sex-phenotype dependent male- and female-biased sDMRs, we tested the developmental dynamics of sex bias in liver methylation and the impacts of mutations in the androgen receptor, estrogen receptor alpha, or the transcriptional repressor Bcl6 gene. True hermaphrodites that carry both unilateral ovaries and contralateral testes were also tested. Our data show that sex bias in methylation either coincides with or follows sex bias in the expression of sDMR-proximal genes, suggesting that sex bias in gene expression may be required for demethylation at certain sDMRs. Global ablation of AR, ESR1, or a liver-specific loss of BCL6, all alter sDMR methylation, whereas presence of both an ovary and a testis delays the establishment of male-type methylation levels in hermaphrodites. Moreover, the Bcl6-LKO shows dissociation between expression and methylation, suggesting a distinct role of BCL6 in demethylation of intragenic sDMRs.
format	article
author	Najla AlOgayil Klara Bauermeister Jose Hector Galvez Varun S. Venkatesh Qinwei Kim-wee Zhuang Matthew L. Chang Rachel A. Davey Jeffrey D. Zajac Kinuyo Ida Akihide Kamiya Teruko Taketo Guillaume Bourque Anna K. Naumova
author_facet	Najla AlOgayil Klara Bauermeister Jose Hector Galvez Varun S. Venkatesh Qinwei Kim-wee Zhuang Matthew L. Chang Rachel A. Davey Jeffrey D. Zajac Kinuyo Ida Akihide Kamiya Teruko Taketo Guillaume Bourque Anna K. Naumova
author_sort	Najla AlOgayil
title	Distinct roles of androgen receptor, estrogen receptor alpha, and BCL6 in the establishment of sex-biased DNA methylation in mouse liver
title_short	Distinct roles of androgen receptor, estrogen receptor alpha, and BCL6 in the establishment of sex-biased DNA methylation in mouse liver
title_full	Distinct roles of androgen receptor, estrogen receptor alpha, and BCL6 in the establishment of sex-biased DNA methylation in mouse liver
title_fullStr	Distinct roles of androgen receptor, estrogen receptor alpha, and BCL6 in the establishment of sex-biased DNA methylation in mouse liver
title_full_unstemmed	Distinct roles of androgen receptor, estrogen receptor alpha, and BCL6 in the establishment of sex-biased DNA methylation in mouse liver
title_sort	distinct roles of androgen receptor, estrogen receptor alpha, and bcl6 in the establishment of sex-biased dna methylation in mouse liver
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/01f3318d5de14971bc8fe6b025ea3a3a
work_keys_str_mv	AT najlaalogayil distinctrolesofandrogenreceptorestrogenreceptoralphaandbcl6intheestablishmentofsexbiaseddnamethylationinmouseliver AT klarabauermeister distinctrolesofandrogenreceptorestrogenreceptoralphaandbcl6intheestablishmentofsexbiaseddnamethylationinmouseliver AT josehectorgalvez distinctrolesofandrogenreceptorestrogenreceptoralphaandbcl6intheestablishmentofsexbiaseddnamethylationinmouseliver AT varunsvenkatesh distinctrolesofandrogenreceptorestrogenreceptoralphaandbcl6intheestablishmentofsexbiaseddnamethylationinmouseliver AT qinweikimweezhuang distinctrolesofandrogenreceptorestrogenreceptoralphaandbcl6intheestablishmentofsexbiaseddnamethylationinmouseliver AT matthewlchang distinctrolesofandrogenreceptorestrogenreceptoralphaandbcl6intheestablishmentofsexbiaseddnamethylationinmouseliver AT racheladavey distinctrolesofandrogenreceptorestrogenreceptoralphaandbcl6intheestablishmentofsexbiaseddnamethylationinmouseliver AT jeffreydzajac distinctrolesofandrogenreceptorestrogenreceptoralphaandbcl6intheestablishmentofsexbiaseddnamethylationinmouseliver AT kinuyoida distinctrolesofandrogenreceptorestrogenreceptoralphaandbcl6intheestablishmentofsexbiaseddnamethylationinmouseliver AT akihidekamiya distinctrolesofandrogenreceptorestrogenreceptoralphaandbcl6intheestablishmentofsexbiaseddnamethylationinmouseliver AT terukotaketo distinctrolesofandrogenreceptorestrogenreceptoralphaandbcl6intheestablishmentofsexbiaseddnamethylationinmouseliver AT guillaumebourque distinctrolesofandrogenreceptorestrogenreceptoralphaandbcl6intheestablishmentofsexbiaseddnamethylationinmouseliver AT annaknaumova distinctrolesofandrogenreceptorestrogenreceptoralphaandbcl6intheestablishmentofsexbiaseddnamethylationinmouseliver
_version_	1718383792105717760

Distinct roles of androgen receptor, estrogen receptor alpha, and BCL6 in the establishment of sex-biased DNA methylation in mouse liver

Ejemplares similares