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Nucleic Acids Res. 2014 Oct;42(18):11433-46. doi: 10.1093/nar/gku852. Epub 2014 Sep 23.

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

Author information

1
Department of Cancer and Inflammation Research, University of Southern Denmark, Odense, DK-5000, Denmark mgjerstorff@health.sdu.dk.
2
Department of Cancer and Inflammation Research, University of Southern Denmark, Odense, DK-5000, Denmark.
3
Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense, DK-5000, Denmark.
4
Department of Cancer and Inflammation Research, University of Southern Denmark, Odense, DK-5000, Denmark The Lundbeckfonden Center of Excellence NanoCAN, University of Southern Denmark, Odense, DK-5000, Denmark.
5
The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, DK-2200, Denmark.
6
Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200, Denmark.
7
Department of Cancer and Inflammation Research, University of Southern Denmark, Odense, DK-5000, Denmark The Lundbeckfonden Center of Excellence NanoCAN, University of Southern Denmark, Odense, DK-5000, Denmark Department of Oncology, Odense University Hospital, Odense, DK-5000, Denmark.

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.

PMID:
25249625
PMCID:
PMC4191419
DOI:
10.1093/nar/gku852
[Indexed for MEDLINE]
Free PMC Article

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