The non-methylated DNA-binding function of Kaiso is not required in early Xenopus laevis development.
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.
Ruzov
Alexey
A
Human Genetics Unit, MRC, Western General Hospital, Edinburgh, UK.
Savitskaya
Ekaterina
E
Hackett
Jamie A
JA
Reddington
James P
JP
Prokhortchouk
Anna
A
Madej
Monika J
MJ
Chekanov
Nikolai
N
Li
Minghui
M
Dunican
Donncha S
DS
Prokhortchouk
Egor
E
Pennings
Sari
S
Meehan
Richard R
RR
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002645:Chickens; D017124:Conserved Sequence; D018899:CpG Islands; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D054262:Gastrulation / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013045:Species Specificity; D023741:Takifugu; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D029867:Xenopus Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
D018398:Homeodomain Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C093133:SIA1 protein, Xenopus; D014157:Transcription Factors; D051153:Wnt Proteins; D029867:Xenopus Proteins; C451401:ZBTB33 protein, Xenopus; D029961:Zebrafish Proteins; C512785:wnt11b protein, Xenopus; C579532:zbtb4 protein, zebrafish; D004247:DNA