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; Joseph F. Costello

doi:10.1038/ncomms7363

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

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75 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 language	English
Article number	6363
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7363
State	Published - Feb 18 2015

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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, Article 6363. https://doi.org/10.1038/ncomms7363

@article{b65ed84187b0454fa62ad30eb1582b82,

title = "Intermediate DNA methylation is a conserved signature of genome regulation",

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.",

author = "Ginell Elliott and Chibo Hong and Xiaoyun Xing and Xin Zhou and Daofeng Li and Cristian Coarfa and Bell, {Robert J.A.} and Maire, {Cecile L.} and Ligon, {Keith L.} and Mahvash Sigaroudinia and Philippe Gascard and Tlsty, {Thea D.} and Harris, {R. Alan} and Schalkwyk, {Leonard C.} and Misha Bilenky and Jonathan Mill and Farnham, {Peggy J.} and Manolis Kellis and Marra, {Marco A.} and Aleksandar Milosavljevic and Martin Hirst and Stormo, {Gary D.} and Ting Wang and Costello, {Joseph F.}",

year = "2015",

month = feb,

day = "18",

doi = "10.1038/ncomms7363",

language = "English",

volume = "6",

journal = "Nature communications",

issn = "2041-1723",

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Elliott, G, Hong, C, Xing, X, Zhou, X, Li, D, Coarfa, C, Bell, RJA, Maire, CL, Ligon, KL, Sigaroudinia, M, Gascard, P, Tlsty, TD, Harris, RA, Schalkwyk, LC, Bilenky, M, Mill, J, Farnham, PJ, Kellis, M, Marra, MA, Milosavljevic, A, Hirst, M, Stormo, GD, Wang, T & Costello, JF 2015, 'Intermediate DNA methylation is a conserved signature of genome regulation', Nature communications, vol. 6, 6363. https://doi.org/10.1038/ncomms7363

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.

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.

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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 -

Intermediate DNA methylation is a conserved signature of genome regulation

Abstract

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