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ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor-initiating cell state.
Chudnovsky, Yakov; Kim, Dohoon; Zheng, Siyuan; Whyte, Warren A; Bansal, Mukesh; Bray, Mark-Anthony; Gopal, Shuba; Theisen, Matthew A; Bilodeau, Steve; Thiru, Prathapan; Muffat, Julien; Yilmaz, Omer H; Mitalipova, Maya; Woolard, Kevin; Lee, Jeongwu; Nishimura, Riko; Sakata, Nobuo; Fine, Howard A; Carpenter, Anne E; Silver, Serena J; Verhaak, Roel G W; Califano, Andrea; Young, Richard A; Ligon, Keith L; Mellinghoff, Ingo K; Root, David E; Sabatini, David M; Hahn, William C; Chheda, Milan G.
Afiliação
  • Chudnovsky Y; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Kim D; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Zheng S; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Whyte WA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
  • Bansal M; Department of Systems Biology, Columbia University, New York, NY 10032, USA; Center for Computational Biology and Bioinformatics, Columbia University, New York, NY 10032, USA.
  • Bray MA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Gopal S; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Theisen MA; Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Bilodeau S; Centre de Recherche sur le Cancer and Centre de Recherche du CHU de Québec (Hôtel-Dieu de Québec), Université Laval, QC G1R 2J6, Canada; Département de Biologie Moléculaire, Biochimie Médicale et Pathologie, Faculté de Médecine, Université Laval, QC G1R 2J6, Canada.
  • Thiru P; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
  • Muffat J; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
  • Yilmaz OH; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; The David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA.
  • Mitalipova M; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
  • Woolard K; Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
  • Lee J; Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland, OH 44195, USA.
  • Nishimura R; Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan.
  • Sakata N; Department of Biochemistry, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
  • Fine HA; Division of Hematology and Medical Oncology, New York University Cancer Institute, New York University Langone Medical Center, New York, NY 10016, USA; Brain Tumor Center, New York University Cancer Institute, New York University Langone Medical Center, New York, NY 10016, USA.
  • Carpenter AE; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Silver SJ; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Verhaak RG; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Genomic Medicine, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Califano A; Department of Systems Biology, Columbia University, New York, NY 10032, USA; Center for Computational Biology and Bioinformatics, Columbia University, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University, New York, NY 10032, USA; Department of Biochemistry and Molecular
  • Young RA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Ligon KL; Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA.
  • Mellinghoff IK; Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Department of Pharmacology, Weill-Cornell Graduate School of Biomedical Sciences, New York, NY 10021, US
  • Root DE; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Sabatini DM; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; The David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge,
  • Hahn WC; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: william_hahn@dfci.harvard.edu.
  • Chheda MG; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Department of Medical Oncology, Dana-Farbe
Cell Rep ; 6(2): 313-24, 2014 Jan 30.
Article em En | MEDLINE | ID: mdl-24440720
ABSTRACT
Glioblastoma (GBM) harbors subpopulations of therapy-resistant tumor-initiating cells (TICs) that are self-renewing and multipotent. To understand the regulation of the TIC state, we performed an image-based screen for genes regulating GBM TIC maintenance and identified ZFHX4, a 397 kDa transcription factor. ZFHX4 is required to maintain TIC-associated and normal human neural precursor cell phenotypes in vitro, suggesting that ZFHX4 regulates differentiation, and its suppression increases glioma-free survival in intracranial xenografts. ZFHX4 interacts with CHD4, a core member of the nucleosome remodeling and deacetylase (NuRD) complex. ZFHX4 and CHD4 bind to overlapping sets of genomic loci and control similar gene expression programs. Using expression data derived from GBM patients, we found that ZFHX4 significantly affects CHD4-mediated gene expression perturbations, which defines ZFHX4 as a master regulator of CHD4. These observations define ZFHX4 as a regulatory factor that links the chromatin-remodeling NuRD complex and the GBM TIC state.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoantígenos / Fatores de Transcrição / Regulação Neoplásica da Expressão Gênica / Glioblastoma / Proteínas de Homeodomínio / Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoantígenos / Fatores de Transcrição / Regulação Neoplásica da Expressão Gênica / Glioblastoma / Proteínas de Homeodomínio / Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos