Differentiation-responsive elements in the 5' region of the mouse tissue plasminogen activator gene confer two-stage regulation by retinoic acid and cyclic AMP in teratocarcinoma cells.

摘要: F9 cells induced to differentiate with retinoic acid (RA) increase transcription of the tissue plasminogen activator (t-PA) gene. Further treatment these cyclic AMP (cAMP) results in an additional stimulation t-PA gene transcription. To investigate mechanism this two-stage regulation, 4 kilobase pairs (kbp) 5'-flanking sequence from murine was isolated. Two major start sites for were found, neither which depended on a classical TATA motif correct initiation. By using transient transfection assays, it determined that 4-kbp flanking could confer reporter genes same differentiation-specific expression as observed endogenous Deletion analyses fragment showed 190 bp sufficient bestow degree regulation constructs. Within region DNA, analysis revealed possible cAMP regulatory element, CTF/NF-1 recognition sequence, two potential Sp1 sites, and five binding factor AP-2. The deletion experiments, coupled positions cis-acting elements, suggest multiple factors, including those bind CTF/NF-1, Sp1, AP-2 may be involved during cell differentiation.