CYR61 - Gene Structure and Regulation

Gene Structure and Regulation

CYR61 is located at human chromosome 1p22.3, whereas the mouse Cyr61 gene is located at chromosome 3, 72.9cM. The mouse CYR61 coding region spans ~3.2 Kb, containing 5 exons interspaced with 4 introns. The first exon encodes 5’-UTR sequence and the first several amino acids in the secretory signal peptide. The remaining four exons each encode a distinct CCN1 domain. The 5th exon also contains the 3’-UTR sequences, which has 5 copies of AU-rich elements that confers a short mRNA half life, and a mir-155 target site. The CYR61 promoter is a TATA box containing promoter, with binding sites for many transcription factors including AP1, ATF, E2F, HNF3b, NF1, NFκB, SP1, and SRF, and 2 poly(CA) stretches that may form Z-DNA structure. Transcriptional activation of CYR61 is exquisitely sensitive to a wide range of environmental perturbations, including stimulation by platelet-derived growth factor and basic fibroblast growth factor, transforming growth factor β1 (TGF-β1), growth hormone, the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), cAMP, vitamin D3, estrogen and tamoxifen, angiotensin II, hypoxia, UV light, and mechanical stretch.

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