Ski Is Required for Tri-Methylation of H3K9 in Major Satellite and for Repression of Pericentromeric Genes: Mmp3, Mmp10 and Mmp13, in Mouse Fibroblasts

Claudio Cappelli, Hugo Sepulveda, Solange Rivas, Víctor Pola, Ulises Urzúa, Gerardo Donoso, Eduardo Sagredo, David Carrero, Emmanuel Casanova-Ortiz, Alfredo Sagredo, Marisel González, Marcia Manterola, Gino Nardocci, Ricardo Armisén, Martin Montecino, Katherine Marcelain

Research output: Contribution to journalArticlepeer-review

Abstract

Several mechanisms directing a rapid transcriptional reactivation of genes immediately after mitosis have been described. However, little is known about the maintenance of repressive signals during mitosis. In this work, we address the role of Ski in the repression of gene expression during M/G1 transition in mouse embryonic fibroblasts (MEFs). We found that Ski localises as a distinct pair of dots at the pericentromeric region of mitotic chromosomes, and the absence of the protein is related to high acetylation and low tri-methylation of H3K9 in pericentromeric major satellite. Moreover, differential expression assays in early G1 cells showed that the presence of Ski is significantly associated with repression of genes localised nearby to pericentromeric DNA. In mitotic cells, chromatin immunoprecipitation assays confirmed the association of Ski to major satellite and the promoters of the most repressed genes: Mmp3, Mmp10 and Mmp13. These genes are at pericentromeric region of chromosome 9. In these promoters, the presence of Ski resulted in increased H3K9 tri-methylation levels. This Ski-dependent regulation is also observed during interphase. Consequently, Mmp activity is augmented in Ski −/− MEFs. Altogether, these data indicate that association of Ski with the pericentromeric region of chromosomes during mitosis is required to maintain the silencing bookmarks of underlying chromatin.

Original languageEnglish
Pages (from-to)3222-3238
Number of pages17
JournalJournal of Molecular Biology
Volume432
Issue number10
DOIs
StatePublished - 1 May 2020
Externally publishedYes

Bibliographical note

Funding Information:
This work was financially supported by the National Commission for Scientific and Technological Research (CONICYT), Chile, through the following Programs: FONDECYT 1151435 and 1120222 ; PIA ACT172101 ; FONDAP 15090007 ; and Chilean doctoral fellowship 21110559.

Publisher Copyright:
© 2020 Elsevier Ltd

Keywords

  • H3K9me3
  • MMP
  • MaSat
  • Ski
  • mitotic bookmarking

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