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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Chudnovsky Y,Kim D,Zheng S,Whyte WA,Bansal M,Bray MA,Gopal S,Theisen MA,Bilodeau S,Thiru P,Muffat J,Yilmaz OH,Mitalipova M,Woolard K,Lee J,Nishimura R,Sakata N,Fine HA,Carpenter AE,Silver SJ,Verhaak RG,Califanodoi
10.1016/j.celrep.2013.12.032subject
Has Abstractpub_date
2014-01-30 00:00:00pages
313-24issue
2issn
2211-1247pii
S2211-1247(13)00790-0journal_volume
6pub_type
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