The CTCF Insulator Protein Is Posttranslationally Modified by SUMO |
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| Authors: | Melissa J MacPherson Linda G Beatty Wenjing Zhou Minjie Du and Paul D Sadowski |
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| Institution: | 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. |
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| Abstract: | 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. |
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