Core promoters: active contributors to combinatorial gene regulation

The studies cited above provide strong evidence that core promoter diversity is an important contributor to combinatorial regulation. In the future, it will be important to subject this hypothesis to more stringent tests. With respect to the study by Butler and Kadonaga (2001) in this issue, it will be important to identify the enhancers that exhibit core promoter preferences, as well as the promoters that may be relevant targets of those enhancers. Evidence that the endogenous core promoters possess the anticipated structures would provide considerable support for the hypothesis. In addition to confirming the importance of core promoter preferences for combinatorial regulation, it will be important to explore in greater depth the mechanistic basis of these preferences. In some respects, this goal will be difficult to achieve until current controversies regarding the basic mechanisms of transcriptional activation have been resolved. On the other hand, because the core promoter preferences of transcriptional activators lead to a number of testable predictions, further exploration of the mechanisms underlying these preferences may contribute to the resolution of the controversies.