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Epigenetic control of female puberty

Lomniczi, A and Loche, A and Castellano, JM and Ronnekleiv, OK and Bosch, M and Kaidar, G and Knoll, JG and Wright, H and Pfeifer, GP and Ojeda, SR (2013) Epigenetic control of female puberty. Nature Neuroscience. pp. 281-289.

Abstract

The timing of puberty is controlled by many genes. The elements coordinating this process have not, however, been identified. Here we show that an epigenetic mechanism of transcriptional repression times the initiation of female puberty in rats. We identify silencers of the Polycomb group (PcG) as principal contributors to this mechanism and show that PcG proteins repress Kiss1, a puberty-activating gene. Hypothalamic expression of two key PcG genes, Eed and Cbx7, decreased and methylation of their promoters increased before puberty. Inhibiting DNA methylation blocked both events and resulted in pubertal failure. The pubertal increase in Kiss1 expression was accompanied by EED loss from the Kiss1 promoter and enrichment of histone H3 modifications associated with gene activation. Preventing the eviction of EED from the Kiss1 promoter disrupted pulsatile gonadotropin-releasing hormone release, delayed puberty and compromised fecundity. Our results identify epigenetic silencing as a mechanism underlying the neuroendocrine control of female puberty. 2013 Nature America, Inc

Item Type: Article
Additional Information: pubid: 87 nvp_institute: NIBR contributor_address: (Lomniczi, Loche, Castellano, Ronnekleiv, Kaidar, Knoll, Wright, Ojeda) Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR, United States (Ronnekleiv, Bosch) Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, OR, United States (Pfeifer) Division of Biology, Beckman Research Institute of the City of Hope, Duarte, CA, United States (Loche) Friedrich Miescher Institute, Biomedical Research Novartis Research Foundation, Basel, Switzerland (Kaidar) Maccabi Health Services, Pardes-Hana, Israel (Knoll) Department of Pediatrics, Oregon Health and Science University, Portland, OR, United States
Date Deposited: 13 Oct 2015 13:13
Last Modified: 29 Jan 2016 00:45
URI: https://oak.novartis.com/id/eprint/21929

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