Epigenomics: mapping the methylome.
DNA methylation is integral to normal development and disease processes. However, the genomic distribution of methylated sequences--the methylome--is poorly understood. We have recently developed a platform technology for rapid assessment of methylation status throughout the human genome in a high-resolution, high-throughput manner. This is achieved by coupling a methylated DNA immunoprecipitation (MeDIP) method for isolating methyl cytosine rich fragments with array-based comparative genomic hybridization (array CGH). Using a combination of whole genome tiling path BAC arrays and CpG island microarrays, DNA methylation profiles are obtained simultaneously at both genome-wide and locus-specific levels. A comparison between male and female DNA using MeDIP-array CGH revealed unexpected hypomethylation of the inactive x-chromosome in gene-poor regions. Furthermore, comparisons between cancer and noncancer cell types yielded differential methylation patterns that link genetic and epigenetic instability offering a new approach to decipher misregulation in cancer. Finally, we provide new data showing epigenomic instability in lung cancer cells with concurrent regions of genetic and epigenetic alterations harboring known oncogenes.
Wilson
Ian M
IM
British Columbia Cancer Research Centre, Vancouver, BC, Canada. wilson@bccrc.ca
Davies
Jonathan J
JJ
Weber
Michael
M
Brown
Carolyn J
CJ
Alvarez
Carlos E
CE
MacAulay
Calum
C
Schübeler
Dirk
D
Lam
Wan L
WL
D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D044127:Epigenesis, Genetic; D023281:Genomics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis
D004273:DNA, Neoplasm