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Conserved role of intragenic DNA methylation in regulating alternative promoters

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  • Alika K. Maunakea

    (Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco
    Present addresses: Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland 20892, USA (A.K.M.); EPFL-ISREC, SV 2818, Station 19, Lausanne 1015, Switzerland (K.S.).)

  • 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
    Present addresses: Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland 20892, USA (A.K.M.); EPFL-ISREC, SV 2818, Station 19, Lausanne 1015, Switzerland (K.S.).)

  • 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
    Howard Hughes Medical Institute, 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
    Center for Genome Sciences and Systems Biology, Washington University)

  • Joseph F. Costello

    (Brain Tumor Research Center, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco)

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.

Suggested Citation

  • 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 & Alle, 2010. "Conserved role of intragenic DNA methylation in regulating alternative promoters," Nature, Nature, vol. 466(7303), pages 253-257, July.
  • Handle: RePEc:nat:nature:v:466:y:2010:i:7303:d:10.1038_nature09165
    DOI: 10.1038/nature09165
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    Cited by:

    1. Nicholas C. Gervais & Rebecca S. Shapiro, 2024. "Discovering the hidden function in fungal genomes," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. David Martino & Nina Kresoje & Nelly Amenyogbe & Rym Ben-Othman & Bing Cai & Mandy Lo & Olubukola Idoko & Oludare A. Odumade & Reza Falsafi & Travis M. Blimkie & Andy An & Casey P. Shannon & Sebastian, 2024. "DNA Methylation signatures underpinning blood neutrophil to lymphocyte ratio during first week of human life," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Chirag Nepal & Jesper B. Andersen, 2023. "Alternative promoters in CpG depleted regions are prevalently associated with epigenetic misregulation of liver cancer transcriptomes," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Rahul Kumar & Prashant Swapnil & Mukesh Meena & Shweta Selpair & Bal Govind Yadav, 2022. "Plant Growth-Promoting Rhizobacteria (PGPR): Approaches to Alleviate Abiotic Stresses for Enhancement of Growth and Development of Medicinal Plants," Sustainability, MDPI, vol. 14(23), pages 1-16, November.

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