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Molecular and Cellular Biology, February 2009, p. 714-725, Vol. 29, No. 3
0270-7306/09/$08.00+0     doi:10.1128/MCB.00825-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The CTCF Insulator Protein Is Posttranslationally Modified by SUMO{triangledown}

Melissa J. MacPherson,1 Linda G. Beatty,1 Wenjing Zhou,2 Minjie Du,3 and Paul D. Sadowski1*

Department of Molecular Genetics, 1 King's College Circle, University of Toronto, Toronto, ON M5S 1A8, Canada,1 the Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, University Health Network, 620 University Avenue, Toronto M5G 2M9, Canada,2 Microbix Biosystems Inc., 341 Bering Avenue, Toronto M8Z 3A8, Canada3

Received 22 May 2008/ Returned for modification 23 June 2008/ Accepted 10 November 2008

The CTCF protein is a highly conserved zinc finger protein that is implicated in many aspects of gene regulation and nuclear organization. Its functions include the ability to act as a repressor of genes, including the c-myc oncogene. In this paper, we show that the CTCF protein can be posttranslationally modified by the small ubiquitin-like protein SUMO. CTCF is SUMOylated both in vivo and in vitro, and we identify two major sites of SUMOylation in the protein. The posttranslational modification of CTCF by the SUMO proteins does not affect its ability to bind to DNA in vitro. SUMOylation of CTCF contributes to the repressive function of CTCF on the c-myc P2 promoter. We also found that CTCF and the repressive Polycomb protein, Pc2, are colocalized to nuclear Polycomb bodies. The Pc2 protein may act as a SUMO E3 ligase for CTCF, strongly enhancing its modification by SUMO 2 and 3. These studies expand the repertoire of posttranslational modifications of CTCF and suggest roles for such modifications in its regulation of epigenetic states.

* Corresponding author. Mailing address: Department of Molecular Genetics, Medical Sciences Building, Room 4284, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada. Phone: (416) 978-6061. Fax: (416) 978-6885. E-mail: p.sadowski{at}utoronto.ca

{triangledown} Published ahead of print on 24 November 2008.

Molecular and Cellular Biology, February 2009, p. 714-725, Vol. 29, No. 3
0270-7306/09/$08.00+0     doi:10.1128/MCB.00825-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Matafora, V., D'Amato, A., Mori, S., Blasi, F., Bachi, A. (2009). Proteomics Analysis of Nucleolar SUMO-1 Target Proteins upon Proteasome Inhibition. Mol. Cell. Proteomics 8: 2243-2255 [Abstract] [Full Text]  
  • Kang, H., Lieberman, P. M. (2009). Cell Cycle Control of Kaposi's Sarcoma-Associated Herpesvirus Latency Transcription by CTCF-Cohesin Interactions. J. Virol. 83: 6199-6210 [Abstract] [Full Text]  
  • Zlatanova, J., Caiafa, P. (2009). CTCF and its protein partners: divide and rule?. J. Cell Sci. 122: 1275-1284 [Abstract] [Full Text]  


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