@article{b2a4c457a48d495bb9c65673c45fba47,
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.",
author = "Yakov Chudnovsky and Dohoon Kim and Siyuan Zheng and Whyte, {Warren A.} and Mukesh Bansal and Bray, {Mark Anthony} and Shuba Gopal and Theisen, {Matthew A.} and Steve Bilodeau and Prathapan Thiru and Julien Muffat and Yilmaz, {Omer H.} and Maya Mitalipova and Kevin Woolard and Jeongwu Lee and Riko Nishimura and Nobuo Sakata and Fine, {Howard A.} and Carpenter, {Anne E.} and Silver, {Serena J.} and Verhaak, {Roel G.W.} and Andrea Califano and Young, {Richard A.} and Ligon, {Keith L.} and Mellinghoff, {Ingo K.} and Root, {David E.} and Sabatini, {David M.} and Hahn, {William C.} and Chheda, {Milan G.}",
note = "Funding Information: We thank members of the D.M.S., W.C.H., and I.K.M. laboratories for advice; members of the H.A.F., Kornblum, and K.L.L. laboratories for advice on work with GBM TICs; C. Maire for technical assistance; L. Solomon, L. Gaffney, and T. DiCesare for extensive graphical help preparing manuscript figures; E. Spooner for mass spectrometric analysis; and H. Le, S. Ponduru, M. Vokes, V. Ljosa, A. Papallo, and other members of the RNAi and Imaging Platforms at the Broad Institute for assistance with RNAi screening and analysis. This work was supported in part by an American Cancer Society postdoctoral fellowship and an American Brain Tumor Association Discovery Grant to Y.C.; grants from the National Institutes of Health (NIH; P30CA016672 and U24CA143883) to S.Z. and R.G.W.V.; a grant from the European Leukodystrophy Association to J.M.; a grant from MEXT/JSPS (KAKENHI 25670168) to N.S.; a grant from the NIH (R01GM089652) and funding from the Broad Institute to A.E.C.; grants from the NIH (U01CA168426 and U54CA121852) to A.C. and M.B.; grants from the NIH (R01HG002668 and R01CA146455) to R.A.Y.; grants from the NIH (R01CA170592 and P01CA095616), Sontag Foundation, and Goldhirsh Foundation to K.L.L.; a grant from the NIH (R01NS080944) to I.K.M.; a grant from the NIH (R01CA129105) and awards from the Starr Foundation, Koch Institute Research Program, Goldhirsh Foundation, and National Brain Tumor Foundation to D.M.S.; grants from the NIH (P01CA095616, P01CA142536, and U01CA176058) to W.C.H.; career development grants from the NIH (K08NS062907 and K12CA090354), an American Brain Tumor Association fellowship, an American Association for Cancer Research/National Brain Tumor Foundation fellowship, and a grant from the Dana-Farber Cancer Institute Pediatric Low Grade Astrocytoma Program to M.G.C.; and a SPARC award from the Broad Institute to D.M.S., W.C.H., and D.E.R. D.M.S. is an investigator of the Howard Hughes Medical Institute. S.J.S. is currently an employee of Novartis. R.A.Y. is a founder of Syros Pharmaceuticals and a member of its board of directors. ",
year = "2014",
doi = "10.1016/j.celrep.2013.12.032",
language = "English",
volume = "6",
pages = "313--324",
journal = "Cell Reports",
issn = "2211-1247",
number = "2",
}