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Cell Rep DOI:10.1016/j.celrep.2013.12.032

ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor-initiating cell state.

Publication TypeJournal Article
Year of Publication2014
AuthorsChudnovsky, Y, Kim, D, Zheng, S, Whyte, WA, Bansal, M, Bray, M-A, Gopal, S, Theisen, MA, Bilodeau, S, Thiru, P, Muffat, J, Yilmaz, ÖH, Mitalipova, M, Woolard, K, Lee, J, Nishimura, R, Sakata, N, Fine, HA, Carpenter, AE, Silver, SJ, Verhaak, RGW, Califano, A, Young, RA, Ligon, KL, Mellinghoff, IK, Root, DE, Sabatini, DM, Hahn, WC, Chheda, MG
JournalCell Rep
Volume6
Issue2
Pages313-24
Date Published2014 Jan 30
ISSN2211-1247
KeywordsAnimals, Autoantigens, Carcinogenesis, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Glioblastoma, Homeodomain Proteins, Humans, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Mice, Inbred NOD, Protein Binding, Transcription Factors, Transcription, Genetic
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.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S2211-1247(13)00790-0
DOI10.1016/j.celrep.2013.12.032
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24440720?dopt=Abstract

Alternate JournalCell Rep
PubMed ID24440720
PubMed Central IDPMC4041390
Grant ListR01NS080944 / NS / NINDS NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
R01CA129105 / CA / NCI NIH HHS / United States
U01CA176058 / CA / NCI NIH HHS / United States
U54CA121852 / CA / NCI NIH HHS / United States
K08 NS062907 / NS / NINDS NIH HHS / United States
R01HG002668 / HG / NHGRI NIH HHS / United States
K99 AG045144 / AG / NIA NIH HHS / United States
U01 CA168426 / CA / NCI NIH HHS / United States
P01 CA095616 / CA / NCI NIH HHS / United States
P30CA016672 / CA / NCI NIH HHS / United States
R01GM089652 / GM / NIGMS NIH HHS / United States
P01 CA142536 / CA / NCI NIH HHS / United States
P01CA142536 / CA / NCI NIH HHS / United States
K12 CA090354 / CA / NCI NIH HHS / United States
R01CA170592 / CA / NCI NIH HHS / United States
R01CA146455 / CA / NCI NIH HHS / United States
R01 NS080944 / NS / NINDS NIH HHS / United States
U01CA168426 / CA / NCI NIH HHS / United States
U24CA143883 / CA / NCI NIH HHS / United States
K08NS062907 / NS / NINDS NIH HHS / United States
R01 GM089652 / GM / NIGMS NIH HHS / United States
U54 CA121852 / CA / NCI NIH HHS / United States
R01 CA170592 / CA / NCI NIH HHS / United States
U01 CA176058 / CA / NCI NIH HHS / United States
P01CA095616 / CA / NCI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
K12CA090354 / CA / NCI NIH HHS / United States
R01 CA129105 / CA / NCI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States
R01 HG002668 / HG / NHGRI NIH HHS / United States