A conserved TN8TCCT motif in the octapeptide-encoding region of Pax genes which has the potential to direct cytosine methylation.
Our previous findings have shown that the developmental genes Pax7 and Pax3 are differentially methylated; the gene region that encodes the paired domain is hypomethylated, whereas the region that encodes the homeodomain is hypermethylated. For this reason, the known DNA sequence between the paired and homeoboxes was analysed for the presence of a conserved DNA motif to which a modifying protein could bind in order to direct the methylation or demethylation of surrounding gene sequences. The octapeptide-encoding region was found to contain several nucleotides that were highly conserved throughout the Pax gene family from phylogenetically distant species. The most conserved nucleotides are thought to comprise a motif TN8TCCT where N8=any combination of eight nucleotides. A conserved octapeptide-like-encoding sequence containing the TN8TCCT motif was also found in non-Pax genes of higher eukaryotes and in the non-coding strand of plants. Moreover, differential methylation seems to be associated with the presence of the TN8TCCT motif in p53 and the human oestrogen receptor genes. The presence of the TN8TCCT motif within an octapeptide-like-encoding sequence in human T-cell leukaemia virus type 1 might suggest that the putative recognition motif may have been introduced into various host genomes via some form of retroviral agent.
Ziman
M R
MR
Department of Pathology, The University of Western Australia, Nedlands, Western Australia, 6009, Australia.
Kay
P H
PH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D003596:Cytosine / Q000378:metabolism*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D016158:Genes, p53; D018398:Homeodomain Proteins; D006801:Humans; D005810:Multigene Family; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins; D051763:PAX7 Transcription Factor; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D011960:Receptors, Estrogen; D015534:Trans-Activators; D003596:Cytosine