Putative zinc finger protein binding sites are over-represented in the boundaries of methylation-resistant CpG islands in the human genome.
BACKGROUND
Majority of CpG dinucleotides in mammalian genomes tend to undergo DNA methylation, but most CpG islands are resistant to such epigenetic modification. Understanding about mechanisms that may lead to the methylation resistance of CpG islands is still very poor.


RESULTS
Using the genome-scale in vivo DNA methylation data from human brain, we investigated the flanking sequence features of methylation-resistant CpG islands, and discovered that there are several over-represented putative Transcription Factor Binding Sites (TFBSs) in methylation-resistant CpG islands, and a specific group of zinc finger protein binding sites are over-represented in boundary regions ( approximately 400 bp) flanking such CpG islands. About 77% of the over-represented putative TFBSs are conserved among human, mouse and rat. We also observed the enrichment of 4 histone methylations in methylation-resistant CpG islands or their boundaries.


CONCLUSIONS
Our results suggest a possible mechanism that certain putative zinc finger protein binding sites over-represented in the boundary regions of the methylation-resistant CpG islands may block the spreading of methylation into these islands, and those TFBSs over-represented within the islands may both reinforce the methylation blocking and promote transcription. Some histone modifications may also enhance the immunity of the CpG islands against DNA methylation by augmenting these TFs' binding. We speculate that the dynamical equilibrium between methylation spreading and blocking is likely to be responsible for the establishment and maintenance of the relatively stable DNA methylation pattern in human somatic cells.
Fan
Shicai
S
MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST, Department of Automation, Tsinghua University, Beijing 100084, China.
Fang
Fang
F
Zhang
Xuegong
X
Zhang
Michael Q
MQ
D000818:Animals; D001665:Binding Sites; D018899:CpG Islands; D019175:DNA Methylation; D015894:Genome, Human; D006801:Humans; D016335:Zinc Fingers