| Literature DB >> 24440720 |
Yakov Chudnovsky1, Dohoon Kim2, Siyuan Zheng3, Warren A Whyte4, Mukesh Bansal5, Mark-Anthony Bray6, Shuba Gopal6, Matthew A Theisen7, Steve Bilodeau8, Prathapan Thiru4, Julien Muffat4, Omer H Yilmaz9, Maya Mitalipova4, Kevin Woolard10, Jeongwu Lee11, Riko Nishimura12, Nobuo Sakata13, Howard A Fine14, Anne E Carpenter6, Serena J Silver6, Roel G W Verhaak15, Andrea Califano16, Richard A Young2, Keith L Ligon17, Ingo K Mellinghoff18, David E Root6, David M Sabatini19, William C Hahn20, Milan G Chheda21.
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.Entities:
Mesh：
Substances：
Year: 2014 PMID： 24440720 PMCID： PMC4041390 DOI： 10.1016/j.celrep.2013.12.032
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423