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

doi:10.1038/ncomms10195

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

Oregon National Primate Research Center

Research output: Contribution to journal › Article › peer-review

61 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 language	English (US)
Article number	10195
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms10195
State	Published - Dec 16 2015

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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@article{488ed2d5847d4449aa1f1ac7c604bad6,

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.",

author = "Alejandro Lomniczi and Hollis Wright and Castellano, {Juan Manuel} and Valerie Matagne and Toro, {Carlos A.} and Suresh Ramaswamy and Plant, {Tony M.} and Ojeda, {Sergio R.}",

note = "Funding Information: We thank Ms Maria Costa for performing the immunohistofluorescence studies. This work was supported by grants from NIH (5RO1 HD013254, U54 HD008610) to T.M.P., the US National Science Foundation (NSF: IOS1121691) to S.R.O., and a Marie Curie International Outgoing Fellowship within the seventh European Community Framework Programme (FP7-PEOPLE-2010-IOF) to J.M.C., C.A.T. and H.W. were supported by NIH Training grant T32 HD007133. H.W. was also supported by NIH Training grant T32 DK00768023. We also thank the staff of the Primate and Assay Cores of the Pittsburgh Specialized Cooperative Centers Program in Reproduction and Infertility for their help with conducting the experiments with male monkeys and for running the RIAs for monkey gonadotropins.",

year = "2015",

month = dec,

day = "16",

doi = "10.1038/ncomms10195",

language = "English (US)",

volume = "6",

journal = "Nature communications",

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T1 - Epigenetic regulation of puberty via Zinc finger protein-mediated transcriptional repression

AU - Lomniczi, Alejandro

AU - Wright, Hollis

AU - Castellano, Juan Manuel

AU - Matagne, Valerie

AU - Toro, Carlos A.

AU - Ramaswamy, Suresh

AU - Plant, Tony M.

AU - Ojeda, Sergio R.

N1 - Funding Information: We thank Ms Maria Costa for performing the immunohistofluorescence studies. This work was supported by grants from NIH (5RO1 HD013254, U54 HD008610) to T.M.P., the US National Science Foundation (NSF: IOS1121691) to S.R.O., and a Marie Curie International Outgoing Fellowship within the seventh European Community Framework Programme (FP7-PEOPLE-2010-IOF) to J.M.C., C.A.T. and H.W. were supported by NIH Training grant T32 HD007133. H.W. was also supported by NIH Training grant T32 DK00768023. We also thank the staff of the Primate and Assay Cores of the Pittsburgh Specialized Cooperative Centers Program in Reproduction and Infertility for their help with conducting the experiments with male monkeys and for running the RIAs for monkey gonadotropins.

PY - 2015/12/16

Y1 - 2015/12/16

N2 - 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.

AB - 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.

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JO - Nature communications

JF - Nature communications

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ER -

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

Abstract

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