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Nat Commun. 2015 Feb 18;6:6363. doi: 10.1038/ncomms7363.

Intermediate DNA methylation is a conserved signature of genome regulation.

Author information

1
Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, Missouri 63108, USA.
2
Brain Tumor Research Center, Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California 94115, USA.
3
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
4
1] Brain Tumor Research Center, Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California 94115, USA [2] Institute for Human Genetics, University of California San Francisco, San Francisco, California 94158, USA.
5
Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
6
Department of Pathology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California 94115, USA.
7
School of Biological Sciences, University of Essex, Colchester CO4 3SQ, UK.
8
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.
9
1] Social Genetic &Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London WC2R 2LS, UK [2] University of Exeter Medical School, Exeter University, St Luke's Campus, Exeter EX1 2LU, UK.
10
Department of Pharmacology and the Genome Center, University of California-Davis, Davis, California 95616, USA.
11
The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
12
1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada [2] Centre for High-Throughput Biology and Department of Microbiology &Immunology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.

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.

PMID:
25691127
PMCID:
PMC4333717
DOI:
10.1038/ncomms7363
[Indexed for MEDLINE]
Free PMC Article
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