Intermediate DNA methylation is a conserved signature of genome regulation

GiNell Elliott, Chibo Hong, Xiaoyun Xing, Xin Zhou, Daofeng Li, Cristian Coarfa, Robert J.A. Bell, Cecile L. Maire, Keith L. Ligon, Mahvash Sigaroudinia, Philippe Gascard, Thea D. Tlsty, R. Alan Harris, Leonard C. Schalkwyk, Misha Bilenky, Jonathan Mill, Peggy J. Farnham, Manolis Kellis, Marco A. Marra, Aleksandar Milosavljevic, Martin Hirst, Gary D. Stormo, Ting Wang () and Joseph F. Costello ()
Additional contact information
GiNell Elliott: Center for Genome Sciences and Systems Biology, Washington University School of Medicine
Chibo Hong: Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco
Xiaoyun Xing: Center for Genome Sciences and Systems Biology, Washington University School of Medicine
Xin Zhou: Center for Genome Sciences and Systems Biology, Washington University School of Medicine
Daofeng Li: Center for Genome Sciences and Systems Biology, Washington University School of Medicine
Cristian Coarfa: Baylor College of Medicine
Robert J.A. Bell: Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco
Cecile L. Maire: Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute
Keith L. Ligon: Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute
Mahvash Sigaroudinia: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco
Philippe Gascard: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco
Thea D. Tlsty: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco
R. Alan Harris: Baylor College of Medicine
Leonard C. Schalkwyk: School of Biological Sciences, University of Essex
Misha Bilenky: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency
Jonathan Mill: Social Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London
Peggy J. Farnham: University of California-Davis
Manolis Kellis: The Broad Institute of MIT and Harvard
Marco A. Marra: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency
Aleksandar Milosavljevic: Baylor College of Medicine
Martin Hirst: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency
Gary D. Stormo: Center for Genome Sciences and Systems Biology, Washington University School of Medicine
Ting Wang: Center for Genome Sciences and Systems Biology, Washington University School of Medicine
Joseph F. Costello: Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: Abstract The role of intermediate methylation states in DNA is unclear. Here, to comprehensively identify regions of intermediate methylation and their quantitative relationship with gene activity, we apply integrative and comparative epigenomics to 25 human primary cell and tissue samples. We report 18,452 intermediate methylation regions located near 36% of genes and enriched at enhancers, exons and DNase I hypersensitivity sites. Intermediate methylation regions average 57% methylation, are predominantly allele-independent and are conserved across individuals and between mouse and human, suggesting a conserved function. These regions have an intermediate level of active chromatin marks and their associated genes have intermediate transcriptional activity. Exonic intermediate methylation correlates with exon inclusion at a level between that of fully methylated and unmethylated exons, highlighting gene context-dependent functions. We conclude that intermediate DNA methylation is a conserved signature of gene regulation and exon usage.

Date: 2015
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DOI: 10.1038/ncomms7363

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