Epigenetic regulation of puberty via Zinc finger protein-mediated transcriptional repression

Alejandro Lomniczi, Hollis Wright, Juan Manuel Castellano, Valerie Matagne, Carlos A. Toro, Suresh Ramaswamy, Tony M. Plant, Sergio R. Ojeda

    Research output: Contribution to journalArticle

    41 Scopus citations

    Abstract

    In primates, puberty is unleashed by increased GnRH release from the hypothalamus following an interval of juvenile quiescence. GWAS implicates Zinc finger (ZNF) genes in timing human puberty. Here we show that hypothalamic expression of several ZNFs decreased in agonadal male monkeys in association with the pubertal reactivation of gonadotropin secretion. Expression of two of these ZNFs, GATAD1 and ZNF573, also decreases in peripubertal female monkeys. However, only GATAD1 abundance increases when gonadotropin secretion is suppressed during late infancy. Targeted delivery of GATAD1 or ZNF573 to the rat hypothalamus delays puberty by impairing the transition of a transcriptional network from an immature repressive epigenetic configuration to one of activation. GATAD1 represses transcription of two key puberty-related genes, KISS1 and TAC3, directly, and reduces the activating histone mark H3K4me2 at each promoter via recruitment of histone demethylase KDM1A. We conclude that GATAD1 epitomizes a subset of ZNFs involved in epigenetic repression of primate puberty.

    Original languageEnglish (US)
    Article number10195
    JournalNature communications
    Volume6
    DOIs
    StatePublished - Dec 16 2015

    ASJC Scopus subject areas

    • Chemistry(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Physics and Astronomy(all)

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    Lomniczi, A., Wright, H., Castellano, J. M., Matagne, V., Toro, C. A., Ramaswamy, S., Plant, T. M., & Ojeda, S. R. (2015). Epigenetic regulation of puberty via Zinc finger protein-mediated transcriptional repression. Nature communications, 6, [10195]. https://doi.org/10.1038/ncomms10195