Abstract
Gonadotropin-releasing hormone (GnRH) and kisspeptin neurons are indispensable for reproductive function. This chapter focuses on the epigenetic regulation of the GnRH and kisspeptin (Kiss1) genes in the context of neuronal development, puberty onset, and maintenance of adult reproductive function. Proper function of GnRH and kisspeptin neurons in the hypothalamus requires coordinated embryonic and postnatal maturation. Recent studies indicate that diverse epigenetic phenomena including the formation of chromatin loops, activation of bivalent domains, maintenance of “stable” histone modifications, and DNA methylation, active demethylation, and hydroxymethylation are all involved in epigenetic regulation of these neurons. This chapter focuses on how these epigenetic regulation components interact with each other and which enzymes or binding factors are involved in specific stages of neuronal development or aging. By emphasizing similar epigenetic mechanisms operating within these two peptidergic neuronal populations, we highlight likely targets for future investigations of environmental influences over puberty timing and progression.
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Acknowledgments
The authors express their sincere appreciation for many current and past postdoctoral research fellows, graduate students, and research specialists including Kim L. Keen, who has contributed to research in the Terasawa laboratory as well as Somaja Louis and Jennifer Li, who contributed to research in the Kurian laboratory. This work was supported by the NIH grants, HD011355, HD015344, and HD077447 for ET, ES020878 for JRK, and OD01106 and RR0061 for the WNPRC.
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Key References
Key References
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Clark and Mellon (1995). This is the first paper identifying that the homeodomain transcription factor Oct 1 regulates the GnRH gene transcription.
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Iyer et al. (2011). This is the first paper demonstrating chromatin modifications of GnRH gene expression during neuronal differentiation.
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Kepa et al. (1996a). This is one of the first works to analyze the structure of GnRH gene promoter.
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Kurian et al. (2010a). This is the first paper to demonstrate that epigenetic changes occur during GnRH neuronal maturation.
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Lomniczi et al. (2015). This is a seminal work demonstrating that Zinc finger protein is involved in prepubertal GnRH suppression in non-human primates.
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Messina et al. (2016). This paper identified that microRNAs regulate GnRH gene expression, which correlates with the timing of puberty.
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Kurian, J.R., Terasawa, E. (2020). Epigenetic Regulation of the GnRH and Kiss1 Genes: Developmental Perspectives. In: Wray, S., Blackshaw, S. (eds) Developmental Neuroendocrinology. Masterclass in Neuroendocrinology, vol 9. Springer, Cham. https://doi.org/10.1007/978-3-030-40002-6_9
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