Loss of the INI1 tumor suppressor does not impair the expression of multiple BRG1-dependent genes or the assembly of SWI/SNF enzymes
Loss of the INI1 tumor suppressor does not impair the expression of multiple BRG1-dependent genes or the assembly of SWI/SNF enzymes
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DOI：
10.1038/sj.onc.1207472
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发表时间：
2004-04-22
期刊：
影响因子：
8
通讯作者：
Imbalzano, AN
中科院分区：
文献类型：
--
作者：
Doan, DN;Veal, TM;Imbalzano, AN
INI 1/hSNF 5肿瘤抑制因子是哺乳动物SWI/SNF染色质重塑酶的组成部分，该染色质重塑酶含有SNF 2家族ATP酶BRM（Brahma）或BRG 1（Brahma Related Gene 1），并有助于调节许多基因。酵母SWI/SNF酶的遗传研究显示，当酶的单个或多个组分被删除时，表型相似，表明每个亚基都需要。为了解决INI 1在哺乳动物细胞中SWI/SNF依赖性基因调控中的作用，我们检测了多个BRG 1依赖性组成型表达基因在INI 1缺陷癌细胞系中的表达。至少有一个INI 1缺陷线表达每个基因，和INI 1的重新引入表达水平的影响可以忽略不计。缺乏INI 1也不能阻止干扰素γ（IFNc）介导的CIITA诱导，CIITA是BRG 1依赖性的，GBP-1是BRG 1增强的，重新引入INI 1的影响最小。染色质免疫沉淀实验表明，BRG 1诱导结合CIITA启动子，尽管缺乏INI 1。与INI 1同源物缺失的酵母不同，INI 1缺陷细胞中的SWI/SNF酶基本上是完整的。因此，在人类细胞中，SWI/SNF酶复合物的形成和许多BRG 1依赖性基因的表达与INI 1无关。
The INI1/hSNF5 tumor suppressor is an integral component of mammalian SWI/SNF chromatin remodeling enzymes that contain SNF2 family ATPases BRM (Brahma) or BRG1 (Brahma Related Gene 1) and that contribute to the regulation of many genes. Genetic studies of yeast SWI/SNF enzyme revealed similar phenotypes when single or multiple components of the enzyme were deleted, indicating a requirement for each subunit. To address the contribution of INI1 in the regulation of SWI/SNF-dependent genes in mammalian cells, we examined the expression of multiple BRG1-dependent, constitutively expressed genes in INI1-deficient cancer cell lines. At least one INI1-deficient line expressed each gene, and reintroduction of INI1 had negligible effects on expression levels. Lack of INI1 also did not prevent interferon gamma (IFNc)-mediated induction of CIITA, which is BRG1 dependent, and GBP-1, which is BRG1 enhanced, and reintroduction of INI1 had minimal effects. Chromatin immunoprecipitation experiments revealed that BRG1 inducibly binds to the CIITA promoter despite the absence of INI1. Unlike yeast deleted for the INI1 homologue, SWI/SNF enzymes in INI1-deficient cells were largely intact. Thus in human cells, SWI/SNF enzyme complex formation and the expression of many BRG1-dependent genes are independent of INI1.