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Molecular and Cellular Biology, July 2002, p. 5019-5026, Vol. 22, No. 14
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.14.5019-5026.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Class II Transactivator Requires brahma-Related Gene 1 To Activate Transcription of Major Histocompatibility Complex Class II Genes

Rajini Mudhasani and Joseph D. Fontes*

Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, Ohio 44115

Received 4 December 2001/ Returned for modification 7 February 2002/ Accepted 15 April 2002

The class II 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 II 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 1 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 II genes. The complex is likely recruited to MHC class II promoters, at least in part, by interaction with CIITA.

* Corresponding author. Mailing address: Department of Biological, Geological and Environmental Sciences, Cleveland State University, Rm. SI219, 2399 Euclid Ave., Cleveland, OH 44115. Phone: (216) 523-7199. Fax: (216) 687-6972. E-mail: j.fontes{at}csuohio.edu.

Molecular and Cellular Biology, July 2002, p. 5019-5026, Vol. 22, No. 14
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.14.5019-5026.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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