title: Distribution of CWG and CCWGG in the human genome.
abstract: Expression of the bacterial CG methyltransferase M*HhaI in mammalian cells appears to generate significant biological effects, while biological effects of the expression of the non-CG methyltransferase M*EcoRII in human cells have not been detected. The association of cytosine methylation with the CG site in mammals is also associated with clustering of CG sites near 5' control regions (CG-islands) of human genes.Moreover spontaneous deamination of 5-methylcytosine at these sites is thought to lead to the well known deficiency of CG sites in genomes where endogenous CG methyltransferases are expressed. Since these associations are generally taken to imply a biological function for the CG dinucleotide that is associated with its selective methylation by endogenous DNA methylation systems, we have asked whether or not CWG or CCWGG sites are clustered in regions flanking human genes and whether or not an overall deficiency of CWG or CCWGG occurs in the human genome. Using build 36.1, of the human genome, we inspected the regions flanking the 28,501 well known gene loci in the human genome. Our analysis confirmed the expected clustering of CG sites near the 5' region of known genes and open reading frames. In contrast to the CG site, neither the CWG site nor the CCWGG site recognized by the bacterial methyltransferase M*EcoRII were clustered in any particular region near known genes and open reading frames. Moreover, neither the CCWGG nor the CWG site was depleted in the human genome, again in sharp contrast to the known genomic deficiency of CpG sites. Our findings suggest that in contrast to CG site recognition, human cytosine methyltransferases recognize CWG and CCWGG only at very low frequency if at all.
authors.affiliation: City of Hope National Medical Center and Beckman Research Institute, Duarte, California, USA. Brian.Watson@utah.edu
authors.forename: Brian
authors.initials: B
authors.lastname: Watson
authors.forename: Kristofer
authors.initials: K
authors.lastname: Munson
authors.forename: Jarrod
authors.initials: J
authors.lastname: Clark
authors.forename: Taras
authors.initials: T
authors.lastname: Shevchuk
authors.forename: Steven S
authors.initials: SS
authors.lastname: Smith
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D015257:DNA-Cytosine Methylases / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D016366:Open Reading Frames / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D001426:Bacterial Proteins; C029528:DNA modification methylase EcoRII; C037664:DNA modification methylase HhaI; D015257:DNA-Cytosine Methylases