4.5 Article

The class II transactivator requires brahma-related gene 1 to activate transcription of major histocompatibility complex class II genes

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MOLECULAR AND CELLULAR BIOLOGY
卷 22, 期 14, 页码 5019-5026

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AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.22.14.5019-5026.2002

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  1. NIAID NIH HHS [R01 AI061386] Funding Source: Medline

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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.

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