Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells (Nature Genetics, 37:853-862, August 2005)

報告日期: 2005/11/01
報告時間: 15:10/16:00
報告學生: 陳琮明(英)
講評老師: 洪建中
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Chromosome-wide and promoter-specific analyses identify site of differential DNA methylation in normal and transformed human cells

Nature genetics 37, 853-862 (2005)

Time: 2005/11/01 ~                           Place: Room 602

Speaker: 基醫所博二 陳琮明                           Commentator:洪建中老師

Abstract:

        Reversible methylation of cytosine is a major epigenetic modification in multicellular organism and involved in regulating many cellular processes including embryonic development, X chromosome inactivation, genomic imprinting and chromosome stability. CpG islands are genomic regions consist of CpG dinucleotide clustering and associate with transcriptional regulation. Cytosine methylation in CpG islands result in transcriptional repression either by interfering with transcription factor binding or by inducing a repressive chromatin structure. Aberrant DNA methylation are found to be associated with many human diseases especially in cancer.  Expression levels of both tumor suppressor genes and oncogenes were altered by the DNA methylation in their promoter regions. However, little is known about the whole-genome distribution of DNA methylation. To determinate the whole-genome DNA methylation pattern of primary and transformed cells, an immunocapturing approach was used to enrich methylated DNA and followed by DNA microarray analysis. By using whole-genome microarrays, a global methylation profile at 80-kb resolution was generated and showed that gene-rich regions have higher levels of methylation. Female and male cells had indistinguishable profiles for autosomes but differences on the X chromosome. The inactive X chromosome (Xi) was hypermethylated at only a subset of gene-rich regions and, unexpectedly, overall hypomethylation was relative to its active counterpart. Large genomic segments with hypomethylation in the transformed cell residing in gene-poor areas were also detected. However, analysis of 6,000 CpG islands showed that only a small set of promoters was methylated differentially, suggesting that aberrant methylation of CpG island promoters in malignancy might be less frequent than previously hypothesized.

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