Downregulation of the polycomb-associated methyltransferase ezh2 during maturation of hippocampal neurons is mediated by microRNAs let-7 and miR-124

Laura Guajardo, Rodrigo Aguilar, Fernando J. Bustos, Gino Nardocci, Rodrigo A. Gutiérrez, Brigitte van Zundert, Martin Montecino

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Ezh2 is a catalytic subunit of the polycomb repressive complex 2 (PRC2) which mediates epigenetic gene silencing through depositing the mark histone H3 lysine 27 trimethylation (H3K27me3) at target genomic sequences. Previous studies have demonstrated that Enhancer of Zeste Homolog 2 (Ezh2) was differentially expressed during maturation of hippocampal neurons; in immature neurons, Ezh2 was abundantly expressed, whereas in mature neurons the expression Ezh2 was significantly reduced. Here, we report that Ezh2 is downregulated by microRNAs (miRs) that are expressed during the hippocampal maturation process. We show that, in mature hippocampal neurons, lethal-7 (let-7) and microRNA-124 (miR-124) are robustly expressed and can target cognate motifs at the 3-UTR of the Ezh2 gene sequence to downregulate Ezh2 expression. Together, these data demonstrate that the PRC2 repressive activity during hippocampal maturation is controlled through a post-transcriptional mechanism that mediates Ezh2 downregulation in mature neurons.

Original languageEnglish
Article number8472
Pages (from-to)1-16
Number of pages16
JournalInternational Journal of Molecular Sciences
Volume21
Issue number22
DOIs
StatePublished - 2 Nov 2020
Externally publishedYes

Bibliographical note

Funding Information:
Funding: This research was supported by FONDAP 15090007 (to R.G. and M.M.), FONDECYT 3140418 (to L.G.), FONDECYT 11190998 (to G.N.), FONDECYT 1170878 (to M.M.), FONDECYT 1181645 (to B.v.Z.), CONICYT PIA/BASAL AFB 170005 CARE UC (to B.v.Z.), and Nucleus UNAB DI-4-17/N (to B.v.Z.).

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Ezh2 expression
  • Let-7 and mir-124 in hippocampus
  • MicroRNA-mediated control

Fingerprint

Dive into the research topics of 'Downregulation of the polycomb-associated methyltransferase ezh2 during maturation of hippocampal neurons is mediated by microRNAs let-7 and miR-124'. Together they form a unique fingerprint.

Cite this