ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor-initiating cell state.
ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor-initiating cell state.
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DOI：
10.1016/j.celrep.2013.12.032
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发表时间：
2014-01-30
期刊：
影响因子：
8.8
通讯作者：
Chheda MG
中科院分区：
文献类型：
--
作者：
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;Califano A;Young RA;Ligon KL;Mellinghoff IK;Root DE;Sabatini DM;Hahn WC;Chheda MG
胶质母细胞瘤（GBM）具有自我更新和多能的治疗抗性肿瘤起始细胞（TIC）亚群。为了了解TIC状态的调节，我们进行了基于图像的筛选，以寻找调节GBM TIC维持的基因，并鉴定了ZFHX 4，一种397-kDa的转录因子。ZFHX 4是维持TIC相关的和正常的人神经前体细胞表型所必需的，表明ZFHX 4调节分化，并且其抑制增加颅内异种移植物中的无胶质瘤存活。ZFHX 4与CHD 4相互作用，CHD 4是NuRD（核小体重塑和脱乙酰酶）复合物的核心成员。ZFHX 4和CHD 4结合到重叠的基因组座位组并控制相似的基因表达程序。使用来自GBM患者的表达数据，我们发现ZFHX 4显著影响CHD 4介导的基因表达扰动，这将ZFHX 4定义为CHD 4的主调节因子。这些观察结果将ZFHX 4定义为连接染色质重塑NuRD复合物和GBM TIC状态的调节因子。
Glioblastomas (GBM) harbor 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 NuRD (nucleosome remodeling and deacetylase) 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.
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影响因子：
--
作者：
Halbig KM;Lekven AC;Kunkel GR
通讯作者：
Kunkel GR
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
50.3
作者：
Gargiulo, Gaetano;Cesaroni, Matteo;van Lohuizen, Maarten
通讯作者：
van Lohuizen, Maarten
影响因子：
2
作者：
Hemmi, Kazunori;Ma, Dongping;Tsuchiya, Kayoko
通讯作者：
Tsuchiya, Kayoko
影响因子：
28.2
作者：
Ding, Yu;Hubert, Christopher G.;Paddison, Patrick J.
通讯作者：
Paddison, Patrick J.