Tissue-specific forms of type IX collagen-proteoglycan arise from the use of two widely separated promoters

We demonstrate that the gene encoding an extracellular matrix component contains two widely separated promoters controlling the generation of different transcripts in a tissue-specific fashion. Two transcription start sites, about 20 kilobase pairs apart, in the alpha 1(IX) collagen gene are utilized to generate different forms of a collagen-proteoglycan (collagen IX) in chicken cartilage and cornea. Transcripts from the upstream site encode a large (266 amino acid residues) globular domain at the amino terminus of alpha 1(IX) chains, whereas the transcripts from the downstream site encode chains that lack this globular domain and contain a short alternative sequence. Transcripts from the upstream site are predominantly present in cartilage, and transcripts from the downstream site are predominantly used in cornea. The structural differences in collagen IX molecules that are synthesized as a consequence of the use of these two alternative transcription start sites in the alpha 1(IX) gene are likely to contribute to the differences in the macromolecular organization of the extracellular matrix in cartilage and cornea. Our finding provides a novel clue to answering the general question of what mechanisms are used to generate unique fibrillar patterns in different tissues.