ZFHX4 Interacts with the NuRD Core Member CHD4 and Regulates the Glioblastoma Tumor-Initiating Cell State
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Young_ZFHX4 interacts.pdf
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Author(s)
Chudnovsky, Yakov
Kim, Dohoon
Zheng, Siyuan
Whyte, Warren A.
Bansal, Mukesh
Bray, Mark-Anthony
Gopal, Shuba
Theisen, Matthew A.
Bilodeau, Steve
Thiru, Prathapan
Date Issued
January 2014
Journal
Cell Reports
Publisher
Elsevier B.V.
Citation
Chudnovsky, Yakov, Dohoon Kim, Siyuan Zheng, Warren A. Whyte, Mukesh Bansal, Mark-Anthony Bray, Shuba Gopal, et al. “ZFHX4 Interacts with the NuRD Core Member CHD4 and Regulates the Glioblastoma Tumor-Initiating Cell State.” Cell Reports 6, no. 2 (January 2014): 313–324.
Version
Final published version
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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported License
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2013.12.032
