Regulation of TRPV1 transcription at the rat P2-promoter. TRPV1 P2-promoter contains two tandem GC-box binding sites adjacent to the start site of TRPV1 transcription (arrow). GC-box "a" was found to be essential for transcriptional activation and appears to be the primary regulatory site in the P2-promoter and is co-regulated by factors Sp1 and Sp4. Depending on the cellular environment and potential state of transcription factor abundance/modification, this model proposes factor Sp4 playing a dominant role in the activation of TRPV1 transcription amongst the Sp1-like factors examined in this study. One type of transcription factor activation may arise from the activity of exogenous products of inflammation, such as NGF. Sp1, Sp4 and/or other members of the Sp1-like family (Spx) may also bind to GC-box region "b" providing additional modulation and full transcriptional activation. Classically transcriptional regulation is dynamic and rapidly responds to intrinsic and extrinsic changes of the cellular milieu. It is envisioned that transcriptional control is directed by a combination of protein modifications and/or formation of a multi-protein transcription factor complex to attract and activate RNA polymerase II (not shown). Differing 'sizes' of transcription factors represent their relative contribution to activation of TRPV1 transcription.