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First published online 21 January 2009
doi: 10.1242/dev.025569

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The non-methylated DNA-binding function of Kaiso is not required in early Xenopus laevis development

Alexey Ruzov^1,*, Ekaterina Savitskaya^2,*, Jamie A. Hackett¹, James P. Reddington¹, Anna Prokhortchouk², Monika J. Madej¹, Nikolai Chekanov², Minghui Li³, Donncha S. Dunican¹, Egor Prokhortchouk², Sari Pennings⁴ and Richard R. Meehan^1,

¹ Human Genetics Unit, MRC, Western General Hospital, Edinburgh EH4 2XU, UK.
² Center `Bioengineering', 60-let Oktyabrya 7-1, Moscow, 117312, Russian Federation.
³ Shanghai Biochip Company, No.151 Libing Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai, 201203, China.
⁴ Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.

Author for correspondence (e-mail: r.meehan{at}hgu.mrc.ac.uk)

Accepted 15 December 2008

Mammalian forms of the transcription repressor, Kaiso, can reportedly bind methylated DNA and non-methylated CTGCNA motifs. Here we compare the DNA-binding properties of Kaiso from frog, fish and chicken and demonstrate that only the methyl-CpG-binding function of Kaiso is evolutionarily conserved. We present several independent experimental lines of evidence that the phenotypic abnormalities associated with xKaiso-depleted Xenopus laevis embryos are independent of the putative CTGCNA-dependent DNA-binding function of xKaiso. Our analysis suggests that xKaiso does not play a role in the regulation of either xWnt11 or Siamois, key signalling molecules in the Wnt pathway during X. laevis gastrulation. The major phenotypic defects associated with xKaiso depletion are premature transcription activation before the mid-blastula transition and concomitant activation of a p53-dependent cell-death pathway.

Key words: Evolution, Kaiso, MBT, Siamois, Methyl-CpG binding, Xenopus laevis

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