title: Epigenetic regulation of puberty via Zinc finger protein-mediated transcriptional repression.
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.
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon 97006, USA.
authors.forename: Alejandro
authors.identifier: http://orcid.org/0000-0003-4535-0103
authors.initials: A
authors.lastname: Lomniczi
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon 97006, USA.
authors.forename: Hollis
authors.initials: H
authors.lastname: Wright
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon 97006, USA.|Department of Cell Biology, Physiology and Immunology, University of Cordoba; CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III; and Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Universitario Reina Sofia (HURS), Cordoba 14004, Spain.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Castellano
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon 97006, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Matagne
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon 97006, USA.
authors.forename: Carlos A
authors.identifier: http://orcid.org/0000-0002-7355-7534
authors.initials: CA
authors.lastname: Toro
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Suresh
authors.identifier: http://orcid.org/0000-0003-0963-4715
authors.initials: S
authors.lastname: Ramaswamy
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Tony M
authors.initials: TM
authors.lastname: Plant
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon 97006, USA.
authors.forename: Sergio R
authors.initials: SR
authors.lastname: Ojeda
mesh_terms: D000818:Animals; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic; D005260:Female; D005455:Fluorescent Antibody Technique; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D050980:GATA Transcription Factors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006062:Gonadotropins / Q000378:metabolism; D056466:Histone Demethylases / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D059648:Kisspeptins / Q000235:genetics / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D015287:Neurokinin B / Q000235:genetics / Q000378:metabolism; D011627:Puberty / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D050980:GATA Transcription Factors; C000607596:GATA zinc finger domain containing 1, rat; D006062:Gonadotropins; D059648:Kisspeptins; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D015287:Neurokinin B; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D056466:Histone Demethylases