Polycomb represses a gene network controlling puberty via modulation of histone demethylase Kdm6b expression

Abstract Female puberty is subject to Polycomb Group (PcG)-dependent transcriptional repression. Kiss1, a puberty-activating gene, is a key target of this silencing mechanism. Using a gain-of-function approach and a systems biology strategy we now show that EED, an essential PcG component, acts in t...

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Autores principales:	Hollis Wright, Carlos F. Aylwin, Carlos A. Toro, Sergio R. Ojeda, Alejandro Lomniczi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ae4467b975d841c390296873c72d8528
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spelling	oai:doaj.org-article:ae4467b975d841c390296873c72d85282021-12-02T13:48:53ZPolycomb represses a gene network controlling puberty via modulation of histone demethylase Kdm6b expression10.1038/s41598-021-81689-42045-2322https://doaj.org/article/ae4467b975d841c390296873c72d85282021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81689-4https://doaj.org/toc/2045-2322Abstract Female puberty is subject to Polycomb Group (PcG)-dependent transcriptional repression. Kiss1, a puberty-activating gene, is a key target of this silencing mechanism. Using a gain-of-function approach and a systems biology strategy we now show that EED, an essential PcG component, acts in the arcuate nucleus of the hypothalamus to alter the functional organization of a gene network involved in the stimulatory control of puberty. A central node of this network is Kdm6b, which encodes an enzyme that erases the PcG-dependent histone modification H3K27me3. Kiss1 is a first neighbor in the network; genes encoding glutamatergic receptors and potassium channels are second neighbors. By repressing Kdm6b expression, EED increases H3K27me3 abundance at these gene promoters, reducing gene expression throughout a gene network controlling puberty activation. These results indicate that Kdm6b repression is a basic mechanism used by PcG to modulate the biological output of puberty-activating gene networks.Hollis WrightCarlos F. AylwinCarlos A. ToroSergio R. OjedaAlejandro LomnicziNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hollis Wright Carlos F. Aylwin Carlos A. Toro Sergio R. Ojeda Alejandro Lomniczi Polycomb represses a gene network controlling puberty via modulation of histone demethylase Kdm6b expression
description	Abstract Female puberty is subject to Polycomb Group (PcG)-dependent transcriptional repression. Kiss1, a puberty-activating gene, is a key target of this silencing mechanism. Using a gain-of-function approach and a systems biology strategy we now show that EED, an essential PcG component, acts in the arcuate nucleus of the hypothalamus to alter the functional organization of a gene network involved in the stimulatory control of puberty. A central node of this network is Kdm6b, which encodes an enzyme that erases the PcG-dependent histone modification H3K27me3. Kiss1 is a first neighbor in the network; genes encoding glutamatergic receptors and potassium channels are second neighbors. By repressing Kdm6b expression, EED increases H3K27me3 abundance at these gene promoters, reducing gene expression throughout a gene network controlling puberty activation. These results indicate that Kdm6b repression is a basic mechanism used by PcG to modulate the biological output of puberty-activating gene networks.
format	article
author	Hollis Wright Carlos F. Aylwin Carlos A. Toro Sergio R. Ojeda Alejandro Lomniczi
author_facet	Hollis Wright Carlos F. Aylwin Carlos A. Toro Sergio R. Ojeda Alejandro Lomniczi
author_sort	Hollis Wright
title	Polycomb represses a gene network controlling puberty via modulation of histone demethylase Kdm6b expression
title_short	Polycomb represses a gene network controlling puberty via modulation of histone demethylase Kdm6b expression
title_full	Polycomb represses a gene network controlling puberty via modulation of histone demethylase Kdm6b expression
title_fullStr	Polycomb represses a gene network controlling puberty via modulation of histone demethylase Kdm6b expression
title_full_unstemmed	Polycomb represses a gene network controlling puberty via modulation of histone demethylase Kdm6b expression
title_sort	polycomb represses a gene network controlling puberty via modulation of histone demethylase kdm6b expression
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ae4467b975d841c390296873c72d8528
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Polycomb represses a gene network controlling puberty via modulation of histone demethylase Kdm6b expression

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