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

By Robert S. Illingworth, Alastair R W Kerr, D. DeSousa, H. Jørgensen, P. Ellis, J. Stalker, D. Jackson, C. Clee, R. Plumb, J. Rogers and 4 more. PLoS Biology, 2008

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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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/87f454b36005a61c8686c146a92991e47c90c40a

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Citations in the corpus

Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state (2010, methodology): “As a more direct test, we determined the distribution of meCpG by fractionating whole genomic DNA based on its affinity for an immobilized meCpG-binding domain (Cross et al., 1994; Illingworth et al., 2008).”
DNA methylation landscapes: provocative insights from epigenomics (2008, methodology): “An method to enrich specifically for unmethylated DNA using CXXC affinity purification (CAP; X represents any residue) was also recently introduce”
Genome-wide methylation analysis of human colon cancer reveals similar hypo- and hypermethylation at conserved tissue-specific CpG island shores (2009, background): “Two recent studies identified a relatively small fraction, 4–8%, of CpG islands with tissue-specific methylatio”
Epigenetics and gene expression (2010, background): “More recent work (Illingworth et al., 2008), however, suggests that about half of the CpG islands in the genome are not associated with annotated promoters, but are located within genes (intragenically) or in intergenic locations.”
An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). (2008, background): “It may be associated with expression potentiality or act to suppress spurious transcriptional initiation within actively transcribed genes (Zilberman et al. 2006; Hellman and Chess 2007; Suzuki et al. 2007).”
CpG islands and the regulation of transcription. (2011, positive): “About 17% of orphan CGIs have been found so far in a methylated state, compared with ;3% of CGIs at annotated gene promoters (Illingworth et al. 2008, 2010; Rauch et al. 2009; Maunakea et al. 2010).”
Targets and dynamics of promoter DNA methylation during early mouse development (2010, neutral): “Cytosine methylation is rare at regulatory regions containing CpG islands; however, a small fraction of CpG islands is methylated in somatic cell”
Aberrant epigenetic landscape in cancer: how cellular identity goes awry. (2010, background): “Interestingly, some of these genes represent genetic loci that are essential for development, including HOX and PAX transcription factor family members (Illingworth et al., 2008; Rauch et al., 2009).”
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CpG islands – ‘A rough guide’ (2009, methodology): “Recently, DNA ‘‘methylome” characterisation has been the basis for an increasing number of investigations due to significant advances in analytical technologies [1,2,10,29,60].”