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

Author

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  • Alejandro Lomniczi

    (Oregon National Primate Research Center)

  • Hollis Wright

    (Oregon National Primate Research Center)

  • Juan Manuel Castellano

    (Oregon National Primate Research Center
    Physiology and Immunology, University of Cordoba
    CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III
    Present addresses: Department of Cell Biology, Physiology and Immunology, University of Cordoba)

  • Valerie Matagne

    (Oregon National Primate Research Center
    Present addresses: Department of Cell Biology, Physiology and Immunology, University of Cordoba)

  • Carlos A. Toro

    (Oregon National Primate Research Center)

  • Suresh Ramaswamy

    (Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine)

  • Tony M. Plant

    (Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine)

  • Sergio R. Ojeda

    (Oregon National Primate Research Center)

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.

Suggested Citation

  • Alejandro Lomniczi & Hollis Wright & Juan Manuel Castellano & Valerie Matagne & Carlos A. Toro & Suresh Ramaswamy & Tony M. Plant & Sergio R. Ojeda, 2015. "Epigenetic regulation of puberty via Zinc finger protein-mediated transcriptional repression," Nature Communications, Nature, vol. 6(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms10195
    DOI: 10.1038/ncomms10195
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