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

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.