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43 Combinatorial Regulation at a Mammalian Composite Response Element

Keith R. Yamamoto, David Pearce, Jay Thomas, Jeffrey N. Miner


Transcriptional regulators from different factor families can interact at composite response elements to effect combinatorial control. We describe studies of plfG, a composite element at which the glucocorticoid receptor and AP-1 factors interact and either enhance or repress transcription, depending on the subunit composition of AP-1. Three general conclusions emerge: (1) Very closely related members of a regulatory factor family can be functionally distinguished at a composite element; (2) discrete “composite specificity domains” can be localized within a particular factor that distinguish it from other members of the same family in the context of a given element and cell type; and (3) the DNA sequence to which a factor binds may affect factor conformation, in turn serving as a determinant of subsequent protein-protein interactions.

The positions and rates of transcription initiation by RNA polymerase II are specified in part by two classes of DNA sequence elements: promoters, which influence the composition and activity of the basal transcription machinery, and response elements, which bind protein factors that sense physiological signals and modulate positively or negatively the efficiency of initiation from linked promoters; response elements and promoters can be interdigitated or widely separated on the DNA. In this chapter, we consider the implications of two generalities that have emerged from studies of response elements and the regulatory factors that bind to them. First, response elements are commonly aggregates of recognition sequences for multiple sequence-specific regulatory factors. In principle, such clustered binding sites for regulatory factors could serve as junction points...

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