Epigenetic control of female puberty

Alejandro Lomniczi, Alberto Loche, Juan Manuel Castellano, Oline Ronnekleiv, Martha Bosch, Gabi Kaidar, J. Gabriel Knoll, Hollis Wright, Gerd P. Pfeifer, Sergio Ojeda

Research output: Contribution to journalArticle

136 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)281-289
Number of pages9
JournalNature Neuroscience
Volume16
Issue number3
DOIs
StatePublished - Mar 2013

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Puberty
Epigenomics
Histone Code
Polycomb-Group Proteins
Delayed Puberty
Genes
DNA Methylation
Gonadotropin-Releasing Hormone
Histones
Methylation
Transcriptional Activation
Fertility

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Epigenetic control of female puberty. / Lomniczi, Alejandro; Loche, Alberto; Castellano, Juan Manuel; Ronnekleiv, Oline; Bosch, Martha; Kaidar, Gabi; Knoll, J. Gabriel; Wright, Hollis; Pfeifer, Gerd P.; Ojeda, Sergio.

In: Nature Neuroscience, Vol. 16, No. 3, 03.2013, p. 281-289.

Research output: Contribution to journalArticle

Lomniczi, A, Loche, A, Castellano, JM, Ronnekleiv, O, Bosch, M, Kaidar, G, Knoll, JG, Wright, H, Pfeifer, GP & Ojeda, S 2013, 'Epigenetic control of female puberty', Nature Neuroscience, vol. 16, no. 3, pp. 281-289. https://doi.org/10.1038/nn.3319
Lomniczi A, Loche A, Castellano JM, Ronnekleiv O, Bosch M, Kaidar G et al. Epigenetic control of female puberty. Nature Neuroscience. 2013 Mar;16(3):281-289. https://doi.org/10.1038/nn.3319
Lomniczi, Alejandro ; Loche, Alberto ; Castellano, Juan Manuel ; Ronnekleiv, Oline ; Bosch, Martha ; Kaidar, Gabi ; Knoll, J. Gabriel ; Wright, Hollis ; Pfeifer, Gerd P. ; Ojeda, Sergio. / Epigenetic control of female puberty. In: Nature Neuroscience. 2013 ; Vol. 16, No. 3. pp. 281-289.
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