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Molecular and Cellular Biology, April 2002, p. 2620-2631, Vol. 22, No. 8
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.8.2620-2631.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Inducer-Specific Enhanceosome Formation Controls Tumor Necrosis Factor Alpha Gene Expression in T Lymphocytes

Alla V. Tsytsykova and Anne E. Goldfeld*

The Center for Blood Research and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115

Received 1 November 2001/ Returned for modification 8 January 2002/ Accepted 25 January 2002

We present evidence that the inducer-specific regulation of the human tumor necrosis factor alpha (TNF-{alpha}) gene in T cells involves the assembly of distinct higher-order transcription enhancer complexes (enhanceosomes), which is dependent upon inducer-specific helical phasing relationships between transcription factor binding sites. While ATF-2, c-Jun, and the coactivator proteins CBP/p300 play a central role in TNF-{alpha} gene activation stimulated by virus infection or intracellular calcium flux, different sets of activators including NFATp, Sp1, and Ets/Elk are recruited to a shared set of transcription factor binding sites depending upon the particular stimulus. Thus, these studies demonstrate that the inducer-specific assembly of unique enhanceosomes is a general mechanism by which a single gene is controlled in response to different extracellular stimuli.

* Corresponding author. Mailing address: The Center for Blood Research and Department of Medicine, Harvard Medical School, 800 Huntington Ave., Boston, MA 02115. Phone: (617) 278-3351. Fax: (617) 278-3454. E-mail: goldfeld{at}cbr.med.harvard.edu.

Molecular and Cellular Biology, April 2002, p. 2620-2631, Vol. 22, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.8.2620-2631.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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