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 MilosavljevicMartin Hirst, Gary D. Stormo, Ting Wang, Joseph F. Costello

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Article number6363
JournalNature Communications
Volume6
DOIs
StatePublished - Feb 18 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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    Elliott, G., Hong, C., Xing, X., Zhou, X., Li, D., Coarfa, C., Bell, R. J. A., Maire, C. L., Ligon, K. L., Sigaroudinia, M., Gascard, P., Tlsty, T. D., Harris, R. A., Schalkwyk, L. C., Bilenky, M., Mill, J., Farnham, P. J., Kellis, M., Marra, M. A., ... Costello, J. F. (2015). Intermediate DNA methylation is a conserved signature of genome regulation. Nature Communications, 6, [6363]. https://doi.org/10.1038/ncomms7363