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H3K27M in Gliomas Causes a One-Step Decrease in H3K27 Methylation and Reduced Spreading within the Constraints of H3K36 Methylation.
Harutyunyan, Ashot S; Chen, Haifen; Lu, Tianyuan; Horth, Cynthia; Nikbakht, Hamid; Krug, Brian; Russo, Caterina; Bareke, Eric; Marchione, Dylan M; Coradin, Mariel; Garcia, Benjamin A; Jabado, Nada; Majewski, Jacek.
Afiliación
  • Harutyunyan AS; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Department of Pediatrics, McGill University, Montreal, QC H4A 3J1, Canada; The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
  • Chen H; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada.
  • Lu T; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Quantitative Life Sciences Program, McGill University, Montreal, QC H3A 2A7, Canada.
  • Horth C; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada.
  • Nikbakht H; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada.
  • Krug B; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada.
  • Russo C; Department of Pediatrics, McGill University, Montreal, QC H4A 3J1, Canada; The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
  • Bareke E; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada.
  • Marchione DM; Department of Biochemistry and Biophysics and the Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Coradin M; Department of Biochemistry and Biophysics and the Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Garcia BA; Department of Biochemistry and Biophysics and the Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Jabado N; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Department of Pediatrics, McGill University, Montreal, QC H4A 3J1, Canada; The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada. Electronic address: nada.jabado@mcgill.ca.
  • Majewski J; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill Genome Centre, Montreal, QC H3A 0G1, Canada. Electronic address: jacek.majewski@mcgill.ca.
Cell Rep ; 33(7): 108390, 2020 11 17.
Article en En | MEDLINE | ID: mdl-33207202
ABSTRACT
The discovery of H3K27M mutations in pediatric gliomas marked a new chapter in cancer epigenomics. Numerous studies have investigated the effect of this mutation on H3K27 trimethylation, but only recently have we started to realize its additional effects on the epigenome. Here, we use isogenic glioma H3K27M+/- cell lines to investigate H3K27 methylation and its interaction with H3K36 and H3K9 modifications. We describe a "step down" effect of H3K27M on the distribution of H3K27 methylation me3 is reduced to me2, me2 is reduced to me1, whereas H3K36me2/3 delineates the boundaries for the spread of H3K27me marks. We also observe a replacement of H3K27me2/3 silencing by H3K9me3. Using a computational simulation, we explain our observations by reduced effectiveness of PRC2 and constraints imposed on the deposition of H3K27me by antagonistic H3K36 modifications. Our work further elucidates the effects of H3K27M in gliomas as well as the general principles of deposition in H3K27 methylation.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Histonas / Glioma Tipo de estudio: Etiology_studies Límite: Humans Idioma: En Revista: Cell Rep Año: 2020 Tipo del documento: Article País de afiliación: Canadá
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Histonas / Glioma Tipo de estudio: Etiology_studies Límite: Humans Idioma: En Revista: Cell Rep Año: 2020 Tipo del documento: Article País de afiliación: Canadá