Ezh1 and Ezh2 differentially regulate PSD-95 gene transcription in developing hippocampal neurons

Mol Cell Neurosci. 2013 Nov;57:130-43. doi: 10.1016/j.mcn.2013.07.012. Epub 2013 Aug 8.

Abstract

Polycomb Repressive Complex 2 (PRC2) mediates transcriptional silencing by catalyzing histone H3 lysine 27 trimethylation (H3K27me3), but its role in the maturation of postmitotic mammalian neurons remains largely unknown. We report that the PRC2 paralogs Ezh1 and Ezh2 are differentially expressed during hippocampal development. We show that depletion of Ezh2 leads to increased expression of PSD-95, a critical plasticity gene, and that reduced PSD-95 gene transcription is correlated with enrichment of Ezh2 at the PSD-95 gene promoter; however, the H3K27me3 epigenetic mark is not present at the PSD-95 gene promoter, likely due to the antagonizing effects of the H3S28P and H3K27Ac marks and the activity of the H3K27 demethylases JMJD3 and UTX. In contrast, increased PSD-95 gene transcription is accompanied by the presence of Ezh1 and elongation-engaged RNA Polymerase II complexes at the PSD-95 gene promoter, while knock-down of Ezh1 reduces PSD-95 transcription. These results indicate that Ezh1 and Ezh2 have antagonistic roles in regulating PSD-95 transcription.

Keywords: 4′,6-diamidino-2-phenylindole; ANOVA; Aldh1L1; AraC; ChIP; DAPI; DIV; EGS; Eed; Ezh1; Ezh1/2; Ezh2; GAPDH; HDAC2; JMJD3; Neuron; PRC1/2; PSD-95; PVDF; PcG; Polycomb Repressive Complex 1/2; RNA Pol II; RNA polymerase II; S.E.M; Suz12; UTX; aldehyde dehydrogenase 1 family, member L1; analysis of variance; chromatin immunoprecipitation; cytosine arabinoside; days in vitro; embryonic ectoderm development; enhancer of zeste homolog 1/2; ethylene glycol-bis(succinic acid N-hydroxysuccinimide ester); glyceraldehyde 3-phosphate dehydrogenase; histone deacetylase 2; jumonji domain-containing protein 3; polycomb group protein; polyvinylidene difluoride; standard error of the mean; suppressor of zeste 12; ubiquitously transcribed tetratricopeptide repeat, X chromosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disks Large Homolog 4 Protein
  • Enhancer of Zeste Homolog 2 Protein
  • Epigenesis, Genetic
  • Gene Expression Regulation, Developmental*
  • Hippocampus / cytology
  • Hippocampus / growth & development
  • Hippocampus / metabolism*
  • Histones / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neurons / metabolism*
  • Polycomb Repressive Complex 2 / genetics
  • Polycomb Repressive Complex 2 / metabolism*
  • Promoter Regions, Genetic
  • Rats
  • Rats, Sprague-Dawley
  • Transcription, Genetic

Substances

  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Histones
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • EZH1 protein, rat
  • EZH2 protein, rat
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2