Transcriptional scaffold: CIITA interacts with NF-Y, RFX, and CREB to cause stereospecific regulation of the class II major histocompatibility complex promoter

Scaffold molecules interact with multiple effecters to elicit specific sign al transduction pathways. CIITA, a non-DNA-binding regulator of class II ma jor histocompatibility complex (MHC) gene transcription, may serve as a tra nscriptional scaffold. Regulation of the class II MHC promoter by CIITA req uires strict spatial-helical arrangements of the X and Y promoter elements. The X element binds RFX (RFX5/RFXANK-RFXB/RFXAP) and CREB, while Y binds N F-Y/CBF (NF-YA, NF-YB, and NF-YC). CIITA interacts with all three. In vivo analysis using both N-terminal and C-terminal deletion constructs identifie d critical domains of CIITA that are required for interaction with NF-YB, N F-YC, RFX5, RFXANK/RFXB, and CREB. We propose that binding of NF-Y/CBF, RFX , and CREB by CIITA results in a macromolecular complex which allows transc ription factors to interact with the class II MHC promoter in a spatially a nd helically constrained fashion.