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

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 aff...

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Main Authors: 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-01-01
Series:PLoS Biology
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18232738/?tool=EBI
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author 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
author_facet 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
author_sort Robert Illingworth
collection DOAJ
description 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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spelling doaj.art-33b0f73ece2d4373b071dcf909a6f6312023-05-10T05:30:34ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852008-01-0161e2210.1371/journal.pbio.0060022A novel CpG island set identifies tissue-specific methylation at developmental gene loci.Robert IllingworthAlastair KerrDina DesousaHelle JørgensenPeter EllisJim StalkerDavid JacksonChris CleeRobert PlumbJane RogersSean HumphrayTony CoxCordelia LangfordAdrian BirdCpG 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18232738/?tool=EBI
spellingShingle 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
A novel CpG island set identifies tissue-specific methylation at developmental gene loci.
PLoS Biology
title A novel CpG island set identifies tissue-specific methylation at developmental gene loci.
title_full A novel CpG island set identifies tissue-specific methylation at developmental gene loci.
title_fullStr A novel CpG island set identifies tissue-specific methylation at developmental gene loci.
title_full_unstemmed A novel CpG island set identifies tissue-specific methylation at developmental gene loci.
title_short A novel CpG island set identifies tissue-specific methylation at developmental gene loci.
title_sort novel cpg island set identifies tissue specific methylation at developmental gene loci
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18232738/?tool=EBI
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