The polycomb repressive complex 2 is a potential target of SUMO modifications

Eva Madi Riising, Roberto Boggio, Susanna Chiocca, Kristian Helin, Diego Pasini

Research output: Contribution to journalArticle

Abstract

Background: The polycomb Repressive Complex 2 (PRC2) functions as a transcriptional repressor through a mechanism that involves methylation of Histone H3 at lysine 27. The PRC2 complex activity is essential for cellular proliferation, development, and cell fate decisions. PRC2 target genes include important regulators of development and proliferation as well as tumor suppressor genes. Consistent with this, the activity of several Polycomb group (PcG) proteins is deregulated in human cancer suggesting an important role for PcGs in tumor development. Whereas the downstream functions of PcGs are well characterized, the mechanisms of their recruitment to target genes and the regulation of their activity are not fully understood. Principal Findings: Here we show that the two PRC2 components SUZ12 and EZH2 are sumoylated in vitro and in vivo. Among several putative sumoylation sites we have mapped the major site of SUZ12 sumoylation. Furthermore, we show that SUZ12 interacts with the E2-conjugating enzyme UBC9 both in vitro and in vivo and that mutation of the SUZ12 sumoylation site does not abolish this binding. Finally, we provide evidence that the E3-ligase PIASXβ interacts and enchances the sumoylation of SUZ12 in vivo suggesting that PIASXβ could function as an E3-ligase for SUZ12. Conclusions: Taken together, our data identify sumoylation as a novel post-translational modification of components of the PCR2 complex, which could suggest a potential new mechanism to modulate PRC2 repressive activity. Further work aimed to identify the physiological conditions for these modifications will be required to understand the role of SUZ12 and EZH2 sumoylation in PcG-mediated epigenetic regulation of transcription.

Original languageEnglish
Article numbere2704
JournalPLoS One
Volume3
Issue number7
DOIs
Publication statusPublished - Jul 16 2008

Fingerprint

Polycomb Repressive Complex 2
Sumoylation
ligases
neoplasms
tumor suppressor genes
post-translational modification
histones
epigenetics
Ubiquitin-Protein Ligases
methylation
Genes
cell proliferation
lysine
genes
transcription (genetics)
Tumors
mutation
Polycomb-Group Proteins
enzymes
Methylation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

The polycomb repressive complex 2 is a potential target of SUMO modifications. / Riising, Eva Madi; Boggio, Roberto; Chiocca, Susanna; Helin, Kristian; Pasini, Diego.

In: PLoS One, Vol. 3, No. 7, e2704, 16.07.2008.

Research output: Contribution to journalArticle

Riising, Eva Madi ; Boggio, Roberto ; Chiocca, Susanna ; Helin, Kristian ; Pasini, Diego. / The polycomb repressive complex 2 is a potential target of SUMO modifications. In: PLoS One. 2008 ; Vol. 3, No. 7.
@article{7f0ba14ae2de4200b2949aa6ec8d1663,
title = "The polycomb repressive complex 2 is a potential target of SUMO modifications",
abstract = "Background: The polycomb Repressive Complex 2 (PRC2) functions as a transcriptional repressor through a mechanism that involves methylation of Histone H3 at lysine 27. The PRC2 complex activity is essential for cellular proliferation, development, and cell fate decisions. PRC2 target genes include important regulators of development and proliferation as well as tumor suppressor genes. Consistent with this, the activity of several Polycomb group (PcG) proteins is deregulated in human cancer suggesting an important role for PcGs in tumor development. Whereas the downstream functions of PcGs are well characterized, the mechanisms of their recruitment to target genes and the regulation of their activity are not fully understood. Principal Findings: Here we show that the two PRC2 components SUZ12 and EZH2 are sumoylated in vitro and in vivo. Among several putative sumoylation sites we have mapped the major site of SUZ12 sumoylation. Furthermore, we show that SUZ12 interacts with the E2-conjugating enzyme UBC9 both in vitro and in vivo and that mutation of the SUZ12 sumoylation site does not abolish this binding. Finally, we provide evidence that the E3-ligase PIASXβ interacts and enchances the sumoylation of SUZ12 in vivo suggesting that PIASXβ could function as an E3-ligase for SUZ12. Conclusions: Taken together, our data identify sumoylation as a novel post-translational modification of components of the PCR2 complex, which could suggest a potential new mechanism to modulate PRC2 repressive activity. Further work aimed to identify the physiological conditions for these modifications will be required to understand the role of SUZ12 and EZH2 sumoylation in PcG-mediated epigenetic regulation of transcription.",
author = "Riising, {Eva Madi} and Roberto Boggio and Susanna Chiocca and Kristian Helin and Diego Pasini",
year = "2008",
month = "7",
day = "16",
doi = "10.1371/journal.pone.0002704",
language = "English",
volume = "3",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

TY - JOUR

T1 - The polycomb repressive complex 2 is a potential target of SUMO modifications

AU - Riising, Eva Madi

AU - Boggio, Roberto

AU - Chiocca, Susanna

AU - Helin, Kristian

AU - Pasini, Diego

PY - 2008/7/16

Y1 - 2008/7/16

N2 - Background: The polycomb Repressive Complex 2 (PRC2) functions as a transcriptional repressor through a mechanism that involves methylation of Histone H3 at lysine 27. The PRC2 complex activity is essential for cellular proliferation, development, and cell fate decisions. PRC2 target genes include important regulators of development and proliferation as well as tumor suppressor genes. Consistent with this, the activity of several Polycomb group (PcG) proteins is deregulated in human cancer suggesting an important role for PcGs in tumor development. Whereas the downstream functions of PcGs are well characterized, the mechanisms of their recruitment to target genes and the regulation of their activity are not fully understood. Principal Findings: Here we show that the two PRC2 components SUZ12 and EZH2 are sumoylated in vitro and in vivo. Among several putative sumoylation sites we have mapped the major site of SUZ12 sumoylation. Furthermore, we show that SUZ12 interacts with the E2-conjugating enzyme UBC9 both in vitro and in vivo and that mutation of the SUZ12 sumoylation site does not abolish this binding. Finally, we provide evidence that the E3-ligase PIASXβ interacts and enchances the sumoylation of SUZ12 in vivo suggesting that PIASXβ could function as an E3-ligase for SUZ12. Conclusions: Taken together, our data identify sumoylation as a novel post-translational modification of components of the PCR2 complex, which could suggest a potential new mechanism to modulate PRC2 repressive activity. Further work aimed to identify the physiological conditions for these modifications will be required to understand the role of SUZ12 and EZH2 sumoylation in PcG-mediated epigenetic regulation of transcription.

AB - Background: The polycomb Repressive Complex 2 (PRC2) functions as a transcriptional repressor through a mechanism that involves methylation of Histone H3 at lysine 27. The PRC2 complex activity is essential for cellular proliferation, development, and cell fate decisions. PRC2 target genes include important regulators of development and proliferation as well as tumor suppressor genes. Consistent with this, the activity of several Polycomb group (PcG) proteins is deregulated in human cancer suggesting an important role for PcGs in tumor development. Whereas the downstream functions of PcGs are well characterized, the mechanisms of their recruitment to target genes and the regulation of their activity are not fully understood. Principal Findings: Here we show that the two PRC2 components SUZ12 and EZH2 are sumoylated in vitro and in vivo. Among several putative sumoylation sites we have mapped the major site of SUZ12 sumoylation. Furthermore, we show that SUZ12 interacts with the E2-conjugating enzyme UBC9 both in vitro and in vivo and that mutation of the SUZ12 sumoylation site does not abolish this binding. Finally, we provide evidence that the E3-ligase PIASXβ interacts and enchances the sumoylation of SUZ12 in vivo suggesting that PIASXβ could function as an E3-ligase for SUZ12. Conclusions: Taken together, our data identify sumoylation as a novel post-translational modification of components of the PCR2 complex, which could suggest a potential new mechanism to modulate PRC2 repressive activity. Further work aimed to identify the physiological conditions for these modifications will be required to understand the role of SUZ12 and EZH2 sumoylation in PcG-mediated epigenetic regulation of transcription.

UR - http://www.scopus.com/inward/record.url?scp=50549091334&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=50549091334&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0002704

DO - 10.1371/journal.pone.0002704

M3 - Article

C2 - 18628979

AN - SCOPUS:50549091334

VL - 3

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 7

M1 - e2704

ER -