The p120 catenin partner Kaiso is a DNA methylation-dependent transcriptional repressor

  1. Anna Prokhortchouk1,2,
  2. Brian Hendrich2,
  3. Helle Jørgensen2,
  4. Alexei Ruzov1,
  5. Matthias Wilm3,
  6. Georgii Georgiev4,
  7. Adrian Bird2, and
  8. Egor Prokhortchouk1,5,6
  1. 1Group of Transcriptional Control and Oncogenesis, Institute of Gene Biology, Moscow, Russia; 2Wellcome Trust Centre for Cell Biology, Edinburgh University, EH9 3JR Edinburgh, Scotland, UK; 3Protein and Peptide group, EMBL, D-69117 Heidelberg, Germany; 4Department of Molecular Cancer Genetics, Institute of Gene Biology, Moscow, Russia

Abstract

We describe a novel mammalian DNA binding activity that requires at least two symmetrically methylated CpG dinucleotides in its recognition sequence, preferably within the sequence 5′CGCG. A key component of the activity is Kaiso, a protein with POZ and zinc-finger domains that is known to associate with p120 catenin. We find that Kaiso behaves as a methylation-dependent transcriptional repressor in transient transfection assays. Kaiso is a constituent of one of two methyl–CpG binding complexes originally designated as MeCP1. The data suggest that zinc-finger motifs are responsible for DNA binding, and may therefore target repression to specific methylated regions of the genome. As Kaiso associates with p120 catenin, Kaiso may link events at the cell surface with DNA methylation-dependent gene silencing.

Keywords

Footnotes

  • 5 Present address: Wellcome Trust Centre for Cell Biology, Edinburgh University, The King's Buildings, EH9 3JR Edinburgh, UK.

  • 6 Corresponding author.

  • E-MAIL egorbp{at}holyrood.ed.ac.uk; FAX 44-131-650-5379.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.198501.

    • Received January 10, 2001.
    • Accepted May 14, 2001.
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