TY - JOUR
T1 - SSX2 is a novel DNA-binding protein that antagonizes polycomb group body formation and gene repression
AU - Gjerstorff, Morten Frier
AU - Relster, Mette Marie
AU - Greve, Katrine Buch Viden
AU - Moeller, Jesper Bonnet
AU - Elias, Daniel
AU - Lindgreen, Jonas Nørrelund
AU - Schmidt, Steffen
AU - Mollenhauer, Jan
AU - Voldborg, Bjørn
AU - Pedersen, Christina Bøg
AU - Brückmann, Nadine Heidi
AU - Møllegaard, Niels Erik
AU - Ditzel, Henrik Jørn
N1 - © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2014/10/13
Y1 - 2014/10/13
N2 - 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.
AB - 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.
U2 - 10.1093/nar/gku852
DO - 10.1093/nar/gku852
M3 - Journal article
C2 - 25249625
VL - 42
SP - 11433
EP - 11446
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 18
ER -