IDENTIFICATION OF A NOVEL SEQUENCE ELEMENT IN THE COMMON PROMOTER REGION OF HUMAN COLLAGEN TYPE-IV GENES, INVOLVED IN THE REGULATION OF DIVERGENT TRANSCRIPTION

The expression of the heterotrimeric collagen IV molecule alpha1(IV)2a lpha2(IV) is essential for the structural integrity and functional pro perties of all basement membranes. The two genes COL4A1 and COL4A2 tha t code for the subunits are found closely linked on chromosome 13 in a head-to-head arrangement and are transcribed in divergent directions. We have identified a novel trans-acting factor that binds in vitro to a unique homopyrimidine/homopurine stretch within the shared promoter region of the two collagen IV genes. Additional binding sites have be en identified within the first introns of both genes and the consensus sequence CCCTYCCCC for efficient binding has been deduced; the factor was named therefore 'CTC-binding factor' or 'CTCBF'. Mutations in the binding site of CTC-binding factor within the promoter inhibited bind ing in vitro and resulted in reduced transcription from both genes. Th e effect of mutations on the transcription of COL4A2 is more pronounce d than on the transcription of COL4A1. CTC-binding factor is a nuclear factor that binds dominantly in vitro to the collagen IV promoter and is involved in regulating the expression of both collagen IV genes.