The chick type III collagen gene contains two promoters that are preferentially expressed in different cell types and are separated by over 20 kb of DNA containing 23 exons.

Type III collagen is present in prechondrogenic mesenchyme, but not in cartilages formed during endochondral ossification. However, cultured chick chondrocytes contain an unusual transcript of the type III collagen gene in which exons 1-23 are replaced with a previously undescribed exon, 23A; this alternative transcript does not encode type III collagen. This observation suggested that, although production of type III collagen mRNA is repressed in chondrocytes, transcription of the type III collagen gene may continue from an alternative promoter. To test this prediction, we isolated and characterized both the upstream and internal promoters of this gene and tested their ability to direct transcription in chondrocytes and skin fibroblasts. The upstream promoter is active in fibroblasts, but inactive in chondrocytes, indicating that repression of type III collagen synthesis during chondrogenesis is transcriptionally mediated. Additionally, sequences in intron 23, preceding exon 23A, function as a highly active promoter in chondrocytes; transcription from this promoter is repressed in fibroblasts. Thus transcriptional control of the type III collagen gene is highly complex, with two promoters separated by at least 20 kb of DNA that are preferentially expressed in different cell types and give rise to RNAs with different structures and functions.