Polycomb represses a gene network controlling puberty via modulation of histone demethylase Kdm6b expression

• Published in: Scientific reports Vol. 11; no. 1; pp. 1996 - 17
• Main Authors: Wright, Hollis, Aylwin, Carlos F., Toro, Carlos A., Ojeda, Sergio R., Lomniczi, Alejandro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.01.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/2584; 631/378/340; 631/378/87; 692/163/2743/2742; Arcuate nucleus; Functional morphology; Gene expression; Gene silencing; Glutamatergic transmission; Histones; Humanities and Social Sciences; Hypothalamus; multidisciplinary; Polycomb group proteins; Potassium channels; Puberty; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-81689-4

Female puberty is subject to Polycomb Group (PcG)-dependent transcriptional repression. Kiss1 , a puberty-activating gene, is a key target of this silencing mechanism. Using a gain-of-function approach and a systems biology strategy we now show that EED, an essential PcG component, acts in the arcuate nucleus of the hypothalamus to alter the functional organization of a gene network involved in the stimulatory control of puberty. A central node of this network is Kdm6b , which encodes an enzyme that erases the PcG-dependent histone modification H3K27me3. Kiss1 is a first neighbor in the network; genes encoding glutamatergic receptors and potassium channels are second neighbors. By repressing Kdm6b expression, EED increases H3K27me3 abundance at these gene promoters, reducing gene expression throughout a gene network controlling puberty activation. These results indicate that Kdm6b repression is a basic mechanism used by PcG to modulate the biological output of puberty-activating gene networks.