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

ABSTRACT: We report gene expression profiles in the medial basal hypothalami of 28-day-old female rats infected with a lentivirus construct that overexpresses EED and matched controls infected with a GFP-expression construct.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE102471 | GEO | 2020/08/09

REPOSITORIES: GEO

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

Project description: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.

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