Conserved role of intragenic DNA methylation in regulating alternative promoters

Alika K. Maunakea, Raman P. Nagarajan, Mikhail Bilenky, Tracy J. Ballinger, Cletus D’Souza, Shaun D. Fouse, Brett E. Johnson, Chibo Hong, Cydney Nielsen, Yongjun Zhao, Gustavo Turecki, Allen Delaney, Richard Varhol, Nina Thiessen, Ksenya Shchors, Vivi M. Heine, David H. Rowitch, Xiaoyun Xing, Chris Fiore, Maximiliaan Schillebeeckx, Steven J. M. Jones, David Haussler, Marco A. Marra, Martin Hirst, Ting Wang () and Joseph F. Costello ()
Additional contact information
Alika K. Maunakea: Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco
Raman P. Nagarajan: Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco
Mikhail Bilenky: Genome Sciences Centre, BC Cancer Agency, 675 W. 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada
Tracy J. Ballinger: Center for Biomolecular Science and Engineering, University of California
Cletus D’Souza: Genome Sciences Centre, BC Cancer Agency, 675 W. 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada
Shaun D. Fouse: Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco
Brett E. Johnson: Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco
Chibo Hong: Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco
Cydney Nielsen: Genome Sciences Centre, BC Cancer Agency, 675 W. 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada
Yongjun Zhao: Genome Sciences Centre, BC Cancer Agency, 675 W. 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada
Gustavo Turecki: McGill Group for Suicide Studies, Douglas Hospital Research Centre, 6875 LaSalle Blvd, Verdun, Quebec H4H 1R3, Canada
Allen Delaney: Genome Sciences Centre, BC Cancer Agency, 675 W. 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada
Richard Varhol: Genome Sciences Centre, BC Cancer Agency, 675 W. 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada
Nina Thiessen: Genome Sciences Centre, BC Cancer Agency, 675 W. 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada
Ksenya Shchors: University of California San Francisco
Vivi M. Heine: University of California San Francisco
David H. Rowitch: University of California San Francisco
Xiaoyun Xing: Center for Genome Sciences and Systems Biology, Washington University
Chris Fiore: Center for Genome Sciences and Systems Biology, Washington University
Maximiliaan Schillebeeckx: Center for Genome Sciences and Systems Biology, Washington University
Steven J. M. Jones: Genome Sciences Centre, BC Cancer Agency, 675 W. 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada
David Haussler: Center for Biomolecular Science and Engineering, University of California
Marco A. Marra: Genome Sciences Centre, BC Cancer Agency, 675 W. 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada
Martin Hirst: Genome Sciences Centre, BC Cancer Agency, 675 W. 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada
Ting Wang: Center for Biomolecular Science and Engineering, University of California
Joseph F. Costello: Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco

Nature, 2010, vol. 466, issue 7303, 253-257

Abstract: Methylation in the genes DNA methylation plays an important role in the maintenance of cell identity through its effect on gene expression. Methylation of 5′ promoters is known to suppress gene expression, while the role of intragenic DNA methylation — where methylation occurs within the body of a gene itself — has been less extensively studied and remains controversial. A map of DNA methylation from the human brain has now been constructed with unprecedented coverage using next-generation sequencing. Integration of this map with brain tissue ChIP-sequencing for histone methylation, and gene expression in mouse and human, highlights a major role for intragenic methylation in regulating tissue-specific promoters in gene bodies, and a surprisingly minor role in 5′ promoters.

Date: 2010
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DOI: 10.1038/nature09165

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