Global, comparative analysis of tissue-specific promoter CpG methylation.
Understanding cell-type-specific epigenetic codes on a global level is a major challenge after the sequencing of the human genome has been completed. Here we applied methyl-CpG immunoprecipitation (MCIp) to obtain comparative methylation profiles of coding and noncoding genes in three human tissues, testis, brain, and monocytes. Forty-four mainly testis-specific promoters were independently validated using bisulfite sequencing or single-gene MCIp, confirming the results obtained by the MCIp microarray approach. We demonstrate the previously unknown somatic hypermethylation at many CpG-rich, testis-specific gene promoters, in particular in ampliconic areas of the Y chromosome. We also identify a number of miRNA genes showing tissue-specific methylation patterns. The comparison of the obtained tissue methylation profiles with corresponding gene expression data indicates a significant association between tissue-specific promoter methylation and gene expression, not only in CpG-rich promoters. In summary, our study highlights the exceptional epigenetic status of germ-line cells in testis and provides a global insight into tissue-specific DNA methylation patterns.
Schilling
Elmar
E
Department of Hematology and Oncology, University Hospital, 93042 Regensburg, Germany.
Rehli
Michael
M
D001921:Brain / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015894:Genome, Human; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008957:Models, Genetic; D009000:Monocytes / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011401:Promoter Regions, Genetic; D015203:Reproducibility of Results; D013737:Testis / Q000378:metabolism
D035683:MicroRNAs