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

Henriquez, B; Bustos, FJ; Aguilar R.; Becerra, A; Simon F.; Montecino, M.; van Zundert, B

Abstract

Polycomb Repressive Complex 2 (PRO) 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 Ezhl and elongation-engaged RNA Polymerase II complexes at the PSD-95 gene promoter, while knock-down of Ezhl reduces PSD-95 transcription. These results indicate that Ezh1 and Ezh2 have antagonistic roles in regulating PSD-95 transcription. (C) 2013 Elsevier Inc. All rights reserved.

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Título según WOS: Ezh1 and Ezh2 differentially regulate PSD-95 gene transcription in developing hippocampal neurons
Título según SCOPUS: Ezh1 and Ezh2 differentially regulate PSD-95 gene transcription in developing hippocampal neurons
Título de la Revista: MOLECULAR AND CELLULAR NEUROSCIENCE
Volumen: 57
Editorial: ACADEMIC PRESS INC ELSEVIER SCIENCE
Fecha de publicación: 2013
Página de inicio: 130
Página final: 143
Idioma: English
URL: http://linkinghub.elsevier.com/retrieve/pii/S104474311300078X
DOI:

10.1016/j.mcn.2013.07.012

Notas: ISI, SCOPUS - ISI