Leading science, pioneering therapies
CRM Publications

A novel CpG island set identifies tissue-specific methylation at developmental gene loci.

TitleA novel CpG island set identifies tissue-specific methylation at developmental gene loci.
Publication TypeJournal Article
Year of Publication2008
AuthorsIllingworth R, Kerr A, Desousa D, Jørgensen H, Ellis P, Stalker J, Jackson D, Clee C, Plumb R, Rogers J, Humphray S, Cox T, Langford C, Bird A
JournalPLoS Biol
Date Published2008 Jan
KeywordsChromosome Mapping, CpG Islands, DNA Methylation, Female, Gene Expression Regulation, Developmental, Gene Library, Genes, Developmental, Genome, Human, Humans, Male, Organ Specificity, Tissue Distribution

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.

Alternate JournalPLoS Biol.
PubMed ID18232738
PubMed Central IDPMC2214817
Grant List / / Wellcome Trust / United Kingdom
Publication institute