The Human Enhancer Blocker CTC-binding Factor Interacts with the Transcription Factor Kaiso

Pierre-Antoine Defossez 1 Kevin F. Kelly 2 Guillaume J. P. Filion 3 Roberto Pérez-Torrado 3 Frédérique Magdinier 4 Hervé Menoni 4 Curtis Nordgaard 2 Juliet Daniel 2 Eric Gilson 4
1 EDC - Centre épigénétique et destin cellulaire
2 McMaster University [Hamilton, Ontario]
3 DNPG - Dynamique nucléaire et plasticité du génome
4 LBMC - Laboratoire de Biologie Moléculaire de la Cellule
Abstract : CTC-binding factor (CTCF) is a DNA-binding protein of vertebrates that plays essential roles in regulating genome activity through its capacity to act as an enhancer blocker. We performed a yeast two-hybrid screen to identify protein partners of CTCF that could regulate its activity. Using full-length CTCF as bait we recovered Kaiso, a POZ-zinc finger transcription factor, as a specific binding partner. The interaction occurs through a C-terminal region of CTCF and the POZ domain of Kaiso. CTCF and Kaiso are co-expressed in many tissues, and CTCF was specifically co-immu-noprecipitated by several Kaiso monoclonal antibodies from nuclear lysates. Kaiso is a bimodal transcription factor that recognizes methylated CpG dinucleotides or a conserved unmethylated sequence (TNGCAGGA, the Kaiso binding site). We identified one consensus unmethylated Kaiso binding site in close proximity to the CTCF binding site in the human 5-globin insulator. We found, in an insulation assay, that the presence of this Kaiso binding site reduced the enhancer-blocking activity of CTCF. These data suggest that the Kaiso-CTCF interaction negatively regulates CTCF insulator activity.
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Pierre-Antoine Defossez, Kevin F. Kelly, Guillaume J. P. Filion, Roberto Pérez-Torrado, Frédérique Magdinier, et al.. The Human Enhancer Blocker CTC-binding Factor Interacts with the Transcription Factor Kaiso. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2005, 280 (52), pp.43017-43023. ⟨10.1074/jbc.M510802200⟩. ⟨hal-01663916⟩

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