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

doi:10.1093/nar/gku852

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

Transcription, RNA, and Gene Medicine Program

15 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Nucleic Acids Research
Vol/bind	42
Udgave nummer	18
Sider (fra-til)	11433-46
Antal sider	14
ISSN	0305-1048
DOI	https://doi.org/10.1093/nar/gku852
Status	Udgivet - 13 okt. 2014

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10.1093/nar/gku852

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Gjerstorff, M. F., Relster, M. M., Greve, K. B. V., Moeller, J. B., Elias, D., Lindgreen, J. N., Schmidt, S., Mollenhauer, J., Voldborg, B., Pedersen, C. B., Brückmann, N. H., Møllegaard, N. E., & Ditzel, H. J. (2014). SSX2 is a novel DNA-binding protein that antagonizes polycomb group body formation and gene repression. Nucleic Acids Research, 42(18), 11433-46. https://doi.org/10.1093/nar/gku852

Gjerstorff, MF, Relster, MM, Greve, KBV, Moeller, JB, Elias, D, Lindgreen, JN, Schmidt, S, Mollenhauer, J, Voldborg, B, Pedersen, CB, Brückmann, NH, Møllegaard, NE & Ditzel, HJ 2014, 'SSX2 is a novel DNA-binding protein that antagonizes polycomb group body formation and gene repression', Nucleic Acids Research, bind 42, nr. 18, s. 11433-46. https://doi.org/10.1093/nar/gku852

@article{a17c9d039b854f929ff75ef1497f4466,

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

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.",

author = "Gjerstorff, {Morten Frier} and Relster, {Mette Marie} and Greve, {Katrine Buch Viden} and Moeller, {Jesper Bonnet} and Daniel Elias and Lindgreen, {Jonas N{\o}rrelund} and Steffen Schmidt and Jan Mollenhauer and Bj{\o}rn Voldborg and Pedersen, {Christina B{\o}g} and Br{\"u}ckmann, {Nadine Heidi} and M{\o}llegaard, {Niels Erik} and Ditzel, {Henrik J{\o}rn}",

note = "{\textcopyright} The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.",

year = "2014",

month = oct,

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doi = "10.1093/nar/gku852",

language = "English",

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journal = "Nucleic Acids Research",

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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

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

SN - 0305-1048

VL - 42

SP - 11433

EP - 11446

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 18

ER -

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

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