The bovine CYP17 promoter contains a transcriptional regulatory element cooperatively bound by TALE homeodomain proteins

Bovine CYP17 is regulated at the transcriptional level by ACTH acting throu gh the second messenger cAMP in adrenal fasciculata and reticularis cells. Promoter analysis has previously identified two regions, proximal and dista l, within the CYP17 promoter important in the cAMP dependent transcriptiona l regulation of this gene. The proximal (-80 to -40) cAMP responsive sequen ce (CRS2) has been identified as a binding site for Steroidogenic Factor-1 (SF-1)/Ad4BP. The distal region (-243 to -100) is also important for the cA MP transcriptional response as revealed by deletion analysis. Within this d istal region from -243 to -225, an independent cAMP responsive sequence ref erred to as CRS1 has been described. The transcription factors binding CRS1 have been identified as homeodomain transcription factors belonging to an atypical class of homeodomain proteins referred to as TALE. Two families of homeodomain proteins which bind CRS1 are the Pbx and Meis1 families. Prote ins from neither of these families can bind CRS1 individually; however, mem bers of the Pbx family interact with members of the Meis1 family to coopera tively bind this element. CRS1 was the first identified cis-acting target e lement for members of both the Pbx and Meis1 family. Unlike SF-1, these pro teins are not expressed in a steroidogenic tissue-specific manner but rathe r, appear ubiquitous. A current model for the function of these proteins in CYP17 regulation is that they may enhance the cAMP response through the do wnstream SF-1 binding site.