The class II transactivator requires brahma-related gene 1 to activate transcription of major histocompatibility complex class II genes
The class II transactivator requires brahma-related gene 1 to activate transcription of major histocompatibility complex class II genes
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DOI：
10.1128/mcb.22.14.5019-5026.2002
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发表时间：
2002-07-01
影响因子：
5.3
通讯作者：
Fontes, JD
中科院分区：
文献类型：
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作者：
Mudhasani, R;Fontes, JD
11类反式激活因子（CIITA）是主要组织相容性复合体（MHC）II类基因转录的关键调节因子。我们在这里证明，CIITA需要ATP酶亚基的hSWI/SNF复合物，婆罗门相关基因1（BRG-1），激活转录。当引入缺乏BRG-1的细胞系时，CIITA无法激活细胞MHC 11类基因。野生型，但不是ATP结合缺陷的BRG-1蛋白在该细胞系中的重新表达恢复CIITA的能力，以反式激活MHC II类基因的转录。有趣的是，当使用基于质粒的报告基因测定法在BRG-1缺陷细胞系中测定CIITA的活性时，BRG-1不是转录激活所必需的，这表明质粒上的染色质结构使得BRG-1不是必需的。进行免疫共沉淀实验以确定BRG-1和CIITA蛋白在细胞中是否彼此缔合。我们发现，这两种蛋白质共免疫沉淀和CIITA的氨基酸I至140是足够的结合。综上所述，这些数据表明BRG-1和很可能的hSWI/SNF复合物是MHC 11类基因转录所需的。该复合物可能至少部分地通过与CIITA的相互作用被募集到MHC 11类启动子。
The class 11 transactivator (CIITA) is the key regulator of major histocompatibility complex (MHC) class II gene transcription. We demonstrate here that CIITA requires the ATPase subunit of an hSWI/SNF complex, brahma-related gene 1 (BRG-1), to activate transcription. When introduced into a cell line lacking BRG-1, CIITA was unable to activate cellular MHC class 11 genes. Reexpression of the wild-type but not an ATP-binding-deficient BRG-1 protein in this cell line restored the ability of CIITA to transactivate transcription of MHC class II genes. Interestingly, when the activity of CIITA was assayed in the BRG-1-deficient cell line by using a plasmid-based reporter assay, BRG-1 was not required for transcriptional activation, suggesting that the chromatin structure on the plasmid is such that BRG-1 is not necessary. Coimmunoprecipitation experiments were performed to determine if BRG-1 and CIITA proteins associate with each other in cells. We found that the two proteins coimmunoprecipitate and that amino acids I to 140 of CIITA are sufficient for binding. Taken together, these data suggest that BRG-1 and, very likely, an hSWI/SNF complex are required for transcription of MHC class 11 genes. The complex is likely recruited to MHC class 11 promoters, at least in part, by interaction with CIITA.