Your browser doesn't support javascript.
loading
MLL5 Orchestrates a Cancer Self-Renewal State by Repressing the Histone Variant H3.3 and Globally Reorganizing Chromatin.
Gallo, Marco; Coutinho, Fiona J; Vanner, Robert J; Gayden, Tenzin; Mack, Stephen C; Murison, Alex; Remke, Marc; Li, Ren; Takayama, Naoya; Desai, Kinjal; Lee, Lilian; Lan, Xiaoyang; Park, Nicole I; Barsyte-Lovejoy, Dalia; Smil, David; Sturm, Dominik; Kushida, Michelle M; Head, Renee; Cusimano, Michael D; Bernstein, Mark; Clarke, Ian D; Dick, John E; Pfister, Stefan M; Rich, Jeremy N; Arrowsmith, Cheryl H; Taylor, Michael D; Jabado, Nada; Bazett-Jones, David P; Lupien, Mathieu; Dirks, Peter B.
Afiliação
  • Gallo M; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
  • Coutinho FJ; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Vanner RJ; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Gayden T; Departments of Pediatrics and Human Genetics, McGill University and McGill University Health Centre Research Institute, Montreal, QC H3H 1P4, Canada.
  • Mack SC; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland, OH 44195, USA; Laboratory Medicine and P
  • Murison A; Ontario Institute for Cancer Research and Princess Margaret Cancer Centre-University Health Network, Toronto, ON M5G 1L7, Canada.
  • Remke M; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
  • Li R; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
  • Takayama N; Ontario Institute for Cancer Research and Princess Margaret Cancer Centre-University Health Network, Toronto, ON M5G 1L7, Canada.
  • Desai K; Department of Genetics, Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH 03755, USA.
  • Lee L; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
  • Lan X; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Park NI; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Barsyte-Lovejoy D; Ontario Institute for Cancer Research and Princess Margaret Cancer Centre-University Health Network, Toronto, ON M5G 1L7, Canada; Structural Genomics Consortium, Toronto, ON M5G 1L7, Canada.
  • Smil D; Ontario Institute for Cancer Research and Princess Margaret Cancer Centre-University Health Network, Toronto, ON M5G 1L7, Canada; Structural Genomics Consortium, Toronto, ON M5G 1L7, Canada.
  • Sturm D; Division of Pediatric Neurooncology, German Cancer Research Centre (DKFZ), Heidelberg 69120, Germany.
  • Kushida MM; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
  • Head R; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
  • Cusimano MD; Division of Neurosurgery, University of Toronto, Toronto, ON M5S 1A8, Canada; St. Michael's Hospital, Toronto, ON M5B 1W8, Canada.
  • Bernstein M; Division of Neurosurgery, University of Toronto, Toronto, ON M5S 1A8, Canada; Toronto Western Hospital, Toronto, ON M5T 2S8, Canada.
  • Clarke ID; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
  • Dick JE; Ontario Institute for Cancer Research and Princess Margaret Cancer Centre-University Health Network, Toronto, ON M5G 1L7, Canada.
  • Pfister SM; Division of Pediatric Neurooncology, German Cancer Research Centre (DKFZ), Heidelberg 69120, Germany.
  • Rich JN; Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland, OH 44195, USA.
  • Arrowsmith CH; Ontario Institute for Cancer Research and Princess Margaret Cancer Centre-University Health Network, Toronto, ON M5G 1L7, Canada; Structural Genomics Consortium, Toronto, ON M5G 1L7, Canada.
  • Taylor MD; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Division of Neurosurgery, University of Toronto
  • Jabado N; Departments of Pediatrics and Human Genetics, McGill University and McGill University Health Centre Research Institute, Montreal, QC H3H 1P4, Canada.
  • Bazett-Jones DP; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
  • Lupien M; Ontario Institute for Cancer Research and Princess Margaret Cancer Centre-University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada. Electronic address: mlupien@uhnres.utoronto.ca.
  • Dirks PB; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Laboratory Medicine and Pathobiology, University of
Cancer Cell ; 28(6): 715-729, 2015 Dec 14.
Article em En | MEDLINE | ID: mdl-26626085
ABSTRACT
Mutations in the histone 3 variant H3.3 have been identified in one-third of pediatric glioblastomas (GBMs), but not in adult tumors. Here we show that H3.3 is a dynamic determinant of functional properties in adult GBM. H3.3 is repressed by mixed lineage leukemia 5 (MLL5) in self-renewing GBM cells. MLL5 is a global epigenetic repressor that orchestrates reorganization of chromatin structure by punctuating chromosomes with foci of compacted chromatin, favoring tumorigenic and self-renewing properties. Conversely, H3.3 antagonizes self-renewal and promotes differentiation. We exploited these epigenetic states to rationally identify two small molecules that effectively curb cancer stem cell properties in a preclinical model. Our work uncovers a role for MLL5 and H3.3 in maintaining self-renewal hierarchies in adult GBM.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / Neoplasias Encefálicas / Histonas / Glioblastoma / Montagem e Desmontagem da Cromatina / Proteínas de Ligação a DNA / Autorrenovação Celular Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / Neoplasias Encefálicas / Histonas / Glioblastoma / Montagem e Desmontagem da Cromatina / Proteínas de Ligação a DNA / Autorrenovação Celular Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2015 Tipo de documento: Article