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

Raurell-Vila, H and Bosch-Presegue, L and Gonzalez, J and Kane-Goldsmith, N and Casal, C and Brown, JP and Marazuela-Duque, A and Singh, PB and Serrano, L and Vaquero, A (2017) An HP1 isoform-specific feedback mechanism regulates Suv39h1 activity under stress conditions. Epigenetics. ISSN 1559-2308

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Raurell-Vila et al_2016.pdf - Accepted Version
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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.

Item Type: Article
Additional Information: This is an Accepted Manuscript of an article published by Taylor & Francis in Epigenetics on 6th January 2017, available online: http://www.tandfonline.com/10.1080/15592294.2016.1278096
Uncontrolled Keywords: 0604 Genetics, 0601 Biochemistry And Cell Biology, 1101 Medical Biochemistry And Metabolomics
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Divisions: Natural Sciences and Psychology
Publisher: Taylor & Francis
Related URLs:
Date Deposited: 13 Jan 2017 08:58
Last Modified: 14 Sep 2017 06:56
DOI or Identification number: 10.1080/15592294.2016.1278096
URI: http://researchonline.ljmu.ac.uk/id/eprint/5256

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