Differential effects of DNA-binding proteins on bidirectional transcription from the common promoter region of human collagen type IV genes COL4A1 and COL4A2

Expression of the heterotrimeric collagen IV (alpha 1(IV))2 alpha 2(IV) is essential for the structural integrity and functional properties of basement membranes. The genes COL4A1 and COL4A2 coding for both subunits are located close to each other on the same chromosome and are transcribed from a common bidirectional promoter element. Binding of at least three different nuclear proteins could be detected within this promoter, a CCAAT-binding protein, Sp1 and a newly identified factor, designated 'CTCBF'. Mutagenesis of binding sites proved that these factors are essential for the efficient transcription of both genes, but revealed differential gene-specific effects. Therefore, the common promoter region of collagen IV does not represent an equally functional bidirectional element, but may be better understood as two overlapping gene-specific promoters with shared elements.