An HP1 isoform-specific feedback mechanism regulates Suv39h1 activity under stress conditions

Helena Raurell-Vila, Laia Bosch-Presegue, Jessica Gonzalez, Noriko Kane-Goldsmith, Carmen Casal, Jeremy P Brown, Anna Marazuela-Duque, Prim B Singh, Lourdes Serrano, Alejandro Vaquero

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The presence of H3K9me3 and heterochromatin protein 1 (HP1) are hallmarks of heterochromatin conserved in eukaryotes. The spreading and maintenance of H3K9me3 is effected by the functional interplay between the H3K9me3-specific histone methyltransferase Suv39h1 and HP1. This interplay is complex in mammals because the three HP1 isoforms, HP1α, β, and γ, are thought to play a redundant role in Suv39h1-dependent deposition of H3K9me3 in pericentric heterochromatin (PCH). Here, we demonstrate that despite this redundancy, HP1α and, to a lesser extent, HP1γ have a closer functional link to Suv39h1, compared to HP1β. HP1α and γ preferentially interact in vivo with Suv39h1, regulate its dynamics in heterochromatin, and increase Suv39h1 protein stability through an inhibition of MDM2-dependent Suv39h1-K87 polyubiquitination. The reverse is also observed, where Suv39h1 increases HP1α stability compared HP1β and γ. The interplay between Suv39h1 and HP1 isoforms appears to be relevant under genotoxic stress. Specifically, loss of HP1α and γ isoforms inhibits the upregulation of Suv39h1 and H3K9me3 that is observed under stress conditions. Reciprocally, Suv39h1 deficiency abrogates stress-dependent upregulation of HP1α and γ, and enhances HP1β levels. Our work defines a specific role for HP1 isoforms in regulating Suv39h1 function under stress via a feedback mechanism that likely regulates heterochromatin formation.

Original languageEnglish
Pages (from-to)166-175
Number of pages10
JournalEpigenetics
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 2017
Externally publishedYes

Keywords

  • Cell Line
  • Chromatin Assembly and Disassembly
  • Chromosomal Proteins, Non-Histone
  • DNA Damage
  • Feedback, Physiological
  • Histones
  • Humans
  • Methyltransferases
  • Protein Binding
  • Protein Isoforms
  • Protein Stability
  • Repressor Proteins
  • Ubiquitination
  • Journal Article

Fingerprint Dive into the research topics of 'An HP1 isoform-specific feedback mechanism regulates Suv39h1 activity under stress conditions'. Together they form a unique fingerprint.

  • Cite this

    Raurell-Vila, H., Bosch-Presegue, L., Gonzalez, J., Kane-Goldsmith, N., Casal, C., Brown, J. P., Marazuela-Duque, A., Singh, P. B., Serrano, L., & Vaquero, A. (2017). An HP1 isoform-specific feedback mechanism regulates Suv39h1 activity under stress conditions. Epigenetics, 12(2), 166-175. https://doi.org/10.1080/15592294.2016.1278096