Evidence that cytosine residues within 5'-CCTGG-3' pentanucleotides can be methylated in human DNA independently of the methylating system that modifies 5'-CG-3' dinucleotides.
In contrast to the complex sequence specificities of the prokaryotic DNA methylating systems, the mammalian machinery identified thus far methylates cytosine residues within the context of a 5'-CG-3' dinucleotide. To explore the possibility that cytosine residues that do not precede guanine may be independently methylated in mammalian DNA, we have examined a region of the human myogenic gene, Myf-3, which is not targeted by the methylating system that methylates 5'-CG-3' dinucleotides. Our investigations have revealed cytosine methylation within the 5'-CCTGG-3' pentanucleotides specified by the 0.8-kb Myf-3 probe. We have also found that in DNA from neoplastic cells, in which 5'-CG-3' dinucleotides within Myf-3 become abnormally hypermethylated, cytosine residues within 5'-CCTGG-3' pentanucleotides are not methylated. Moreover, methylation of 5'-CCTGG-3' pentanucleotides was not detected within the closely related Myf-4 gene, which is normally 5'-CG-3' hypermethylated. These findings indicate the existence of a system that methylates 5'-CCTGG-3' pentanucleotides independently of the system that methylates cytosine residues within 5'-CG-3' dinucleotides. It is possible that the 5'-CCTGG-3' methylating system influences the fate of foreign integrated DNA.
Franchina
M
M
Department of Pathology, The University of Western Australia, Nedlands, Perth.
Kay
P H
PH
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D003596:Cytosine / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D019175:DNA Methylation; D015342:DNA Probes; D006801:Humans; D017570:MyoD Protein / Q000235:genetics; D009841:Oligonucleotides / Q000737:chemistry* / Q000378:metabolism
D015342:DNA Probes; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D009841:Oligonucleotides; D003596:Cytosine; D004247:DNA