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

Sci Rep. 2021 Jan 21;11(1):1996. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Gene Expression Regulation / genetics
  • Gene Regulatory Networks / genetics
  • Humans
  • Hypothalamus / growth & development
  • Hypothalamus / metabolism
  • Jumonji Domain-Containing Histone Demethylases / genetics*
  • Kisspeptins / genetics*
  • Neurons / metabolism
  • Neurosecretory Systems / growth & development
  • Neurosecretory Systems / metabolism
  • Polycomb Repressive Complex 2 / genetics*
  • Polycomb-Group Proteins / genetics
  • Promoter Regions, Genetic / genetics
  • Puberty / genetics*
  • Puberty / physiology
  • Rats
  • Systems Biology


  • EED protein, human
  • Kiss1 protein, rat
  • Kisspeptins
  • Polycomb-Group Proteins
  • Jumonji Domain-Containing Histone Demethylases
  • Kdm6b protein, rat
  • Polycomb Repressive Complex 2