Nuclear Factor I Regulates Brain Fatty Acid-Binding Protein and Glial Fibrillary Acidic Protein Gene Expression in Malignant Glioma Cell Lines
Nuclear Factor I Regulates Brain Fatty Acid-Binding Protein and Glial Fibrillary Acidic Protein Gene Expression in Malignant Glioma Cell Lines
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DOI：
10.1016/j.jmb.2009.06.041
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发表时间：
2009-08-14
影响因子：
5.6
通讯作者：
Godbout, Roseline
中科院分区：
文献类型：
--
作者：
Brun, Miranda;Coles, Jeffrey E.;Godbout, Roseline
胶质细胞酸性蛋白（GFAP），一种通常在星形胶质细胞中发现的中间丝蛋白，和放射状胶质细胞标志物脑脂肪酸结合蛋白（B-FABP;也称为FABP 7）共表达。在恶性胶质瘤细胞系和肿瘤中。核因子I（NFI）识别位点已在B-FABP和GFAP启动子中被鉴定，并且这两个基因的转录被认为由NFI调节。在这里，我们研究的NFI家族的不同成员在调节内源性和异位B-FABP和GFAP基因转录在人类恶性胶质瘤细胞中的作用。我们通过凝胶位移表明，NFI家族的所有四个成员（NFIA、NFIB、NFIC和NFIX）都与B-FABP和GFAP NFI共有位点结合。过表达的NFI，结合突变分析的NFI共识网站使用报告基因分析，支持的作用，所有四个NFI在调节GFAP和B-FABP基因。敲除单个或组合的NFI揭示了启动子依赖性和启动子上下文依赖性的相互作用模式，并表明NFI家族不同成员之间的串扰。我们的数据表明，NFI家族的转录因子在恶性胶质瘤细胞中的B-FABP和GFAP基因的调控中起着关键作用。(C)2009爱思唯尔有限公司版权所有。
Glial fibrillary acidic protein (GFAP), an intermediate filament protein normally found in astrocytes, and the radial glial marker brain fatty acid-binding protein (B-FABP; also known as FABP7) are co-expressed. in malignant glioma cell lines and tumors. Nuclear factor I (NFI) recognition sites have been identified in the B-FABP and GFAP promoters, and transcription of both genes is believed to be regulated by NFI. Here, we study the role of the different members of the NFI family in regulating endogenous and ectopic B-FABP and GFAP gene transcription in human malignant glioma cells. We show by gel shifts that all four members of the NFI family (NFIA, NFIB, NFIC, and NFIX) bind to B-FABP and GFAP NFI consensus sites. Over-expression of NFIs, in conjunction with mutation analysis of NFI consensus sites using a reporter gene assay, supports a role for all four NFIs in the regulation of the GFAP and B-FABP genes. Knockdown of single or combined NFIs reveals promoter-dependent and promoter-context-dependent interaction patterns and suggests cross talk between the different members of the NFI family. Our data indicate that the NFI family of transcription factors plays a key role in the regulation of both the B-FABP and GFAP genes in malignant glioma cells. (C) 2009 Elsevier Ltd. All rights reserved.