A Novel CpG Island Set Identifies Tissue-Specific Methylation at Developmental Gene Loci

نویسندگان

  • Robert Illingworth
  • Alastair Kerr
  • Dina DeSousa
  • Helle Jørgensen
  • Peter Ellis
  • Jim Stalker
  • David Jackson
  • Chris Clee
  • Robert Plumb
  • Jane Rogers
  • Sean Humphray
  • Tony Cox
  • Cordelia Langford
  • Adrian Bird
چکیده

CpG islands (CGIs) are dense clusters of CpG sequences that punctuate the CpG-deficient human genome and associate with many gene promoters. As CGIs also differ from bulk chromosomal DNA by their frequent lack of cytosine methylation, we devised a CGI enrichment method based on nonmethylated CpG affinity chromatography. The resulting library was sequenced to define a novel human blood CGI set that includes many that are not detected by current algorithms. Approximately half of CGIs were associated with annotated gene transcription start sites, the remainder being intra- or intergenic. Using an array representing over 17,000 CGIs, we established that 6%-8% of CGIs are methylated in genomic DNA of human blood, brain, muscle, and spleen. Inter- and intragenic CGIs are preferentially susceptible to methylation. CGIs showing tissue-specific methylation were overrepresented at numerous genetic loci that are essential for development, including HOX and PAX family members. The findings enable a comprehensive analysis of the roles played by CGI methylation in normal and diseased human tissues.

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عنوان ژورنال:
  • PLoS Biology

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2008