The CTCF insulator protein is posttranslationally modified by SUMO.
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.
MacPherson
Melissa J
MJ
Department of Molecular Genetics, 1 King's College Circle, University of Toronto, Toronto, ON, Canada.
Beatty
Linda G
LG
Zhou
Wenjing
W
Du
Minjie
M
Sadowski
Paul D
PD
D000595:Amino Acid Sequence; D000818:Animals; D000076246:CCCTC-Binding Factor; D022003:Cell Nucleus Structures / Q000378:metabolism; D003546:Cysteine Endopeptidases; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008025:Ligases; D051379:Mice; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism; D063146:Polycomb-Group Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D063146:Polycomb-Group Proteins; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; C117909:SUMO2 protein, human; C492189:SUMO3 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014452:Ubiquitins; D004247:DNA; D044767:Ubiquitin-Protein Ligases; D010450:Endopeptidases; D010447:Peptide Hydrolases; C404512:SENP1 protein, human; C512579:Senp5 protein, human; D003546:Cysteine Endopeptidases; D008025:Ligases; C570427:CBX4 protein, human