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Molecular and Cellular Biology, May 2003, p. 3377-3391, Vol. 23, No. 10
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.10.3377-3391.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Distinct Transcriptional Pathways Regulate Basal and Activated Major Histocompatibility Complex Class I Expression

T. Kevin Howcroft,* Aparna Raval, Jocelyn D. Weissman, Anne Gegonne, and Dinah S. Singer

Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892-1360

Received 14 January 2003/ Accepted 25 February 2003

Transcription of major histocompatibility complex (MHC) class I genes is regulated by both tissue-specific (basal) and hormone/cytokine (activated) mechanisms. Although promoter-proximal regulatory elements have been characterized extensively, the role of the core promoter in mediating regulation has been largely undefined. We report here that the class I core promoter consists of distinct elements that are differentially utilized in basal and activated transcription pathways. These pathways recruit distinct transcription factor complexes to the core promoter elements and target distinct transcription initiation sites. Class I transcription initiates at four major sites within the core promoter and is clustered in two distinct regions: "upstream" (-14 and -18) and "downstream" (+12 and +1). Basal transcription initiates predominantly from the upstream start site region and is completely dependent upon the general transcription factor TAF1 (TAFII250). Activated transcription initiates predominantly from the downstream region and is TAF1 (TAFII250) independent. USF1 augments transcription initiating through the upstream start sites and is dependent on TAF1 (TAFII250), a finding consistent with its role in regulating basal class I transcription. In contrast, transcription activated by the interferon mediator CIITA is independent of TAF1 (TAFII250) and focuses initiation on the downstream start sites. Thus, basal and activated transcriptions of an MHC class I gene target distinct core promoter domains, nucleate distinct transcription initiation complexes and initiate at distinct sites within the promoter. We propose that transcription initiation at the core promoter is a dynamic process in which the mechanisms of core promoter function differ depending on the cellular environment.

* Corresponding author. Mailing address: Experimental Immunology Branch, NCI, Bldg. 10, Rm. 4B-17, NIH, 10 Center Dr., MSC 1360, Bethesda, MD 20892-1360. Phone: (301) 496-9097. Fax: (301) 480-8499. E-mail: howcrofk{at}exchange.nih.gov.

Molecular and Cellular Biology, May 2003, p. 3377-3391, Vol. 23, No. 10
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.10.3377-3391.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kobayashi, A., Watanabe, Y., Akasaka, K., Kokubo, T. (2007). Real-time monitoring of functional interactions between upstream and core promoter sequences in living cells of sea urchin embryos. Nucleic Acids Res 0: gkm519v1-13 [Abstract] [Full Text]  
  • Chen, H., Kilberg, M. S. (2006). Alignment of the Transcription Start Site Coincides with Increased Transcriptional Activity from the Human Asparagine Synthetase Gene Following Amino Acid Deprivation of HepG2 Cells. J. Nutr. 136: 2463-2467 [Abstract] [Full Text]  
  • Gegonne, A., Weissman, J. D., Zhou, M., Brady, J. N., Singer, D. S. (2006). TAF7: A possible transcription initiation check-point regulator. Proc. Natl. Acad. Sci. USA 103: 602-607 [Abstract] [Full Text]  
  • Lee, M. P., Howcroft, K., Kotekar, A., Yang, H. H., Buetow, K. H., Singer, D. S. (2005). ATG deserts define a novel core promoter subclass. Genome Res 15: 1189-1197 [Abstract] [Full Text]  


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