SSX2 is a novel DNA-binding protein that antagonizes polycomb group body formation and gene repression

Morten Frier Gjerstorff, Mette Marie Relster, Katrine Buch Viden Greve, Jesper Bonnet Moeller, Daniel Elias, Jonas Nørrelund Lindgreen, Steffen Schmidt, Jan Mollenhauer, Bjørn Voldborg, Christina Bøg Pedersen, Nadine Heidi Brückmann, Niels Erik Møllegaard, Henrik Jørn Ditzel

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Polycomb group (PcG) complexes regulate cellular identity through epigenetic programming of chromatin. Here, we show that SSX2, a germline-specific protein ectopically expressed in melanoma and other types of human cancers, is a chromatin-associated protein that antagonizes BMI1 and EZH2 PcG body formation and derepresses PcG target genes. SSX2 further negatively regulates the level of the PcG-associated histone mark H3K27me3 in melanoma cells, and there is a clear inverse correlation between SSX2/3 expression and H3K27me3 in spermatogenesis. However, SSX2 does not affect the overall composition and stability of PcG complexes, and there is no direct concordance between SSX2 and BMI1/H3K27me3 presence at regulated genes. This suggests that SSX2 antagonizes PcG function through an indirect mechanism, such as modulation of chromatin structure. SSX2 binds double-stranded DNA in a sequence non-specific manner in agreement with the observed widespread association with chromatin. Our results implicate SSX2 in regulation of chromatin structure and function.

Original languageEnglish
JournalNucleic Acids Research
Volume42
Issue number18
Pages (from-to)11433-11446
ISSN0305-1048
DOIs
Publication statusPublished - 2014

Keywords

  • Cell Line, Tumor
  • Cell Nucleus
  • Chromatin
  • DNA
  • Enhancer of Zeste Homolog 2 Protein
  • Gene Expression Regulation, Neoplastic
  • Histones
  • Humans
  • Melanoma
  • Neoplasm Proteins
  • Polycomb Repressive Complex 1
  • Polycomb Repressive Complex 2
  • Polycomb-Group Proteins
  • Repressor Proteins
  • Spermatogenesis
  • Journal Article
  • Research Support, Non-U.S. Gov't

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