ZFHX4 Interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor-initiating cell state Journal Article


Authors: Chudnovsky, Y.; Kim, D.; Zheng, S.; Whyte, W. A.; Bansal, M.; Bray, M. A.; Gopal, S.; Theisen, M. A.; Bilodeau, S.; Thiru, P.; Muffat, J.; Yilmaz, O. H.; Mitalipova, M.; Woolard, K.; Lee, J.; Nishimura, R.; Sakata, N.; Fine, H. A.; Carpenter, A. E.; Silver, S. J.; Verhaak, R. G. W.; Califano, A.; Young, R. A.; Ligon, K. L.; Mellinghoff, I. K.; Root, D. E.; Sabatini, D. M.; Hahn, W. C.; Chheda, M. G.
Article Title: ZFHX4 Interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor-initiating cell state
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 397kDa transcription factor. ZFHX4 is required to maintain TIC-associated and normal human neural precursor cell phenotypes invitro, 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. © 2014 The Authors.
Journal Title: Cell Reports
Volume: 6
Issue: 2
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2014-01-30
Start Page: 313
End Page: 324
Language: English
DOI: 10.1016/j.celrep.2013.12.032
PROVIDER: scopus
PUBMED: 24440720
PMCID: PMC4041390
DOI/URL:
Notes: Export Date: 2 April 2014 -- Source: Scopus
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  1. Milan Chheda
    5 Chheda