TY - JOUR
T1 - Intermediate DNA methylation is a conserved signature of genome regulation
AU - Elliott, Ginell
AU - Hong, Chibo
AU - Xing, Xiaoyun
AU - Zhou, Xin
AU - Li, Daofeng
AU - Coarfa, Cristian
AU - Bell, Robert J.A.
AU - Maire, Cecile L.
AU - Ligon, Keith L.
AU - Sigaroudinia, Mahvash
AU - Gascard, Philippe
AU - Tlsty, Thea D.
AU - Harris, R. Alan
AU - Schalkwyk, Leonard C.
AU - Bilenky, Misha
AU - Mill, Jonathan
AU - Farnham, Peggy J.
AU - Kellis, Manolis
AU - Marra, Marco A.
AU - Milosavljevic, Aleksandar
AU - Hirst, Martin
AU - Stormo, Gary D.
AU - Wang, Ting
AU - Costello, Joseph F.
N1 - Funding Information:
We thank collaborators in the Reference Epigenome Mapping Centers (REMC), the Epigenome Data Analysis and Coordination Center and NCBI who have generated and processed data used in this project. We thank Jufang Chang and Jeff Milbrandt for providing mouse cortical neuron samples. We acknowledge support from the NIH Roadmap Epigenomics Program, sponsored by the National Institute on Drug Abuse (NIDA) and the National Institute of Environmental Health Sciences (NIEHS). We thank Theresa Kadlecek and Arthur Weiss for processing blood samples. J.F.C. and T.W. are supported by NIH grant 5U01ES017154. G.E. is partly supported by the Chancellor’s Graduate Fellowship Program at the Washington University in St Louis. T.W. and G.E. are also supported by NIH Grant R01HG007354, R01HG007175, R01ES024992 and American Cancer Society grant RSG-14-049-01-DMC. J.F.C. is also supported by NIH R01CA169316.
Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.
PY - 2015/2/18
Y1 - 2015/2/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84923345958&partnerID=8YFLogxK
U2 - 10.1038/ncomms7363
DO - 10.1038/ncomms7363
M3 - Article
C2 - 25691127
AN - SCOPUS:84923345958
SN - 2041-1723
VL - 6
JO - Nature Communications
JF - Nature Communications
M1 - 6363
ER -