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

Area of Science:

• Epigenetics
• Molecular Biology
• Cancer Biology

Background:

• Polycomb group (PcG) complexes are crucial epigenetic regulators maintaining cellular identity.
• Aberrant PcG complex function is implicated in various human cancers, including melanoma.
• The role of SSX2, a germline-specific protein found in cancers, in PcG complex regulation is not well understood.

Purpose of the Study:

• To investigate the role of SSX2 in the regulation of Polycomb group (PcG) complexes.
• To determine how SSX2 affects PcG complex formation, target gene expression, and associated epigenetic marks.
• To elucidate the mechanism by which SSX2 antagonizes PcG function in cancer cells.

Main Methods:

• Chromatin immunoprecipitation (ChIP) assays to assess protein binding and histone marks.
• Western blotting to analyze protein levels and complex composition.
• Quantitative PCR (qPCR) to measure target gene expression.
• DNA binding assays to characterize SSX2-DNA interactions.

Main Results:

• SSX2 is a chromatin-associated protein that antagonizes the formation of BMI1 and EZH2 PcG bodies.
• SSX2 derepresses PcG target genes and negatively regulates H3K27me3 levels in melanoma cells.
• An inverse correlation exists between SSX2/3 expression and H3K27me3 during spermatogenesis.
• SSX2 does not alter the overall composition or stability of PcG complexes.
• SSX2 binds double-stranded DNA non-specifically, suggesting a role in modulating chromatin structure.

Conclusions:

• SSX2 antagonizes PcG complex function through an indirect mechanism, likely involving chromatin structure modulation.
• SSX2's interaction with chromatin and its influence on PcG targets suggest a role in epigenetic regulation.
• These findings implicate SSX2 in the epigenetic reprogramming of chromatin and cellular identity in cancer.