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Insulator dysfunction and oncogene activation in IDH mutant gliomas

Author

Listed:
  • William A. Flavahan

    (Massachusetts General Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard
    Howard Hughes Medical Institute)

  • Yotam Drier

    (Massachusetts General Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard
    Howard Hughes Medical Institute)

  • Brian B. Liau

    (Massachusetts General Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard
    Howard Hughes Medical Institute)

  • Shawn M. Gillespie

    (Massachusetts General Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard
    Howard Hughes Medical Institute)

  • Andrew S. Venteicher

    (Massachusetts General Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard
    Massachusetts General Hospital and Harvard Medical School)

  • Anat O. Stemmer-Rachamimov

    (Massachusetts General Hospital and Harvard Medical School)

  • Mario L. Suvà

    (Massachusetts General Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Bradley E. Bernstein

    (Massachusetts General Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard
    Howard Hughes Medical Institute)

Abstract

An epigenetic mechanism in which gain-of-function IDH mutations promote gliomagenesis by disrupting chromosomal topology is presented, with IDH mutations causing the binding sites of the methylation-sensitive insulator CTCF to become hypermethylated; disruption of a CTCF boundary near the glioma oncogene PDGFRA allows a constitutive enhancer to contact and activate the oncogene aberrantly.

Suggested Citation

  • William A. Flavahan & Yotam Drier & Brian B. Liau & Shawn M. Gillespie & Andrew S. Venteicher & Anat O. Stemmer-Rachamimov & Mario L. Suvà & Bradley E. Bernstein, 2016. "Insulator dysfunction and oncogene activation in IDH mutant gliomas," Nature, Nature, vol. 529(7584), pages 110-114, January.
    • Handle: RePEc:nat:nature:v:529:y:2016:i:7584:d:10.1038_nature16490
    DOI: 10.1038/nature16490
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    Citations

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    Cited by:

    1. Konstantin Okonechnikov & Aylin Camgöz & Owen Chapman & Sameena Wani & Donglim Esther Park & Jens-Martin Hübner & Abhijit Chakraborty & Meghana Pagadala & Rosalind Bump & Sahaana Chandran & Katerina K, 2023. "3D genome mapping identifies subgroup-specific chromosome conformations and tumor-dependency genes in ependymoma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Jamie L. Endicott & Paula A. Nolte & Hui Shen & Peter W. Laird, 2022. "Cell division drives DNA methylation loss in late-replicating domains in primary human cells," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Chong Wang & Xiang Liu & Jun Liang & Yohei Narita & Weiyue Ding & Difei Li & Luyao Zhang & Hongbo Wang & Merrin Man Long Leong & Isabella Hou & Catherine Gerdt & Chang Jiang & Qian Zhong & Zhonghui Ta, 2023. "A DNA tumor virus globally reprograms host 3D genome architecture to achieve immortal growth," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Xiao Ge & Haiyan Huang & Keqi Han & Wangjie Xu & Zhaoxia Wang & Qiang Wu, 2023. "Outward-oriented sites within clustered CTCF boundaries are key for intra-TAD chromatin interactions and gene regulation," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. Vinícius G. Contessoto & Olga Dudchenko & Erez Lieberman Aiden & Peter G. Wolynes & José N. Onuchic & Michele Pierro, 2023. "Interphase chromosomes of the Aedes aegypti mosquito are liquid crystalline and can sense mechanical cues," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    6. Dominic D. G. Owens & Giorgio Anselmi & A. Marieke Oudelaar & Damien J. Downes & Alessandro Cavallo & Joe R. Harman & Ron Schwessinger & Akin Bucakci & Lucas Greder & Sara Ornellas & Danuta Jeziorska , 2022. "Dynamic Runx1 chromatin boundaries affect gene expression in hematopoietic development," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Jia-Yong Zhong & Longjian Niu & Zhuo-Bin Lin & Xin Bai & Ying Chen & Feng Luo & Chunhui Hou & Chuan-Le Xiao, 2023. "High-throughput Pore-C reveals the single-allele topology and cell type-specificity of 3D genome folding," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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