Nature Communications (Mar 2019)
H3K27M induces defective chromatin spread of PRC2-mediated repressive H3K27me2/me3 and is essential for glioma tumorigenesis
- Ashot S. Harutyunyan,
- Brian Krug,
- Haifen Chen,
- Simon Papillon-Cavanagh,
- Michele Zeinieh,
- Nicolas De Jay,
- Shriya Deshmukh,
- Carol C. L. Chen,
- Jad Belle,
- Leonie G. Mikael,
- Dylan M. Marchione,
- Rui Li,
- Hamid Nikbakht,
- Bo Hu,
- Gael Cagnone,
- Warren A. Cheung,
- Abdulshakour Mohammadnia,
- Denise Bechet,
- Damien Faury,
- Melissa K McConechy,
- Manav Pathania,
- Siddhant U. Jain,
- Benjamin Ellezam,
- Alexander G. Weil,
- Alexandre Montpetit,
- Paolo Salomoni,
- Tomi Pastinen,
- Chao Lu,
- Peter W. Lewis,
- Benjamin A. Garcia,
- Claudia L. Kleinman,
- Nada Jabado,
- Jacek Majewski
Affiliations
- Ashot S. Harutyunyan
- Department of Human Genetics, McGill University
- Brian Krug
- Department of Human Genetics, McGill University
- Haifen Chen
- Department of Human Genetics, McGill University
- Simon Papillon-Cavanagh
- Department of Human Genetics, McGill University
- Michele Zeinieh
- Department of Human Genetics, McGill University
- Nicolas De Jay
- Department of Human Genetics, McGill University
- Shriya Deshmukh
- Department of Human Genetics, McGill University
- Carol C. L. Chen
- Department of Human Genetics, McGill University
- Jad Belle
- Department of Human Genetics, McGill University
- Leonie G. Mikael
- Department of Pediatrics, McGill University, and The Research Institute of the McGill University Health Center
- Dylan M. Marchione
- Department of Biochemistry and Biophysics, and Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania
- Rui Li
- Department of Human Genetics, McGill University
- Hamid Nikbakht
- Department of Human Genetics, McGill University
- Bo Hu
- Department of Human Genetics, McGill University
- Gael Cagnone
- Department of Human Genetics, McGill University
- Warren A. Cheung
- Department of Human Genetics, McGill University
- Abdulshakour Mohammadnia
- Department of Human Genetics, McGill University
- Denise Bechet
- Department of Human Genetics, McGill University
- Damien Faury
- Department of Human Genetics, McGill University
- Melissa K McConechy
- Department of Human Genetics, McGill University
- Manav Pathania
- Samantha Dickson Brain Cancer Unit, University College London Cancer Institute
- Siddhant U. Jain
- Department of Biomolecular Chemistry, School of Medicine and Public Health and Wisconsin Institute for Discovery, University of Wisconsin
- Benjamin Ellezam
- Department of Pathology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal
- Alexander G. Weil
- Department of Pediatric Neurosurgery, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal
- Alexandre Montpetit
- McGill University and Genome Quebec Innovation Centre
- Paolo Salomoni
- Samantha Dickson Brain Cancer Unit, University College London Cancer Institute
- Tomi Pastinen
- Department of Human Genetics, McGill University
- Chao Lu
- Department of Genetics and Development, Columbia University Irving Medical Center
- Peter W. Lewis
- Department of Biomolecular Chemistry, School of Medicine and Public Health and Wisconsin Institute for Discovery, University of Wisconsin
- Benjamin A. Garcia
- Department of Biochemistry and Biophysics, and Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania
- Claudia L. Kleinman
- Department of Human Genetics, McGill University
- Nada Jabado
- Department of Human Genetics, McGill University
- Jacek Majewski
- Department of Human Genetics, McGill University
- DOI
- https://doi.org/10.1038/s41467-019-09140-x
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 13
Abstract
Lysine27-to-methionine mutations in histone H3 genes (H3K27M) occur in a subgroup of gliomas and decrease genome-wide H3K27 trimethylation. Here the authors utilise primary H3K27M tumour lines and isogenic CRISPR-edited controls and show that H3K27M induces defective chromatin spread of PRC2-mediated repressive H3K27me2/me3.
