A CAMP-RESPONSIVE ELEMENT REGULATES EXPRESSION OF THE MOUSE STEROID 11-BETA-HYDROXYLASE GENE

  • 25 August 1989
    • journal article
    • research article
    • Vol. 264  (24) , 14011-14015
Abstract
In Y1 mouse adrenocortical tumor cells, expression of steroid 11.beta.-hydroxylase (11.beta.-OHase) is stimulated by cAMP following a delay of 4-6 h. Our results demonstrate that a cAMP-responsive element (CRE) within the 11.beta.-OHase promoter region is a major determinant of this induction. The 5''-flanking sequences from the mouse 11.beta.-OHase gene were placed in front of a human growth hormone reporter gene and transfected into Y1 cells. Treatment of transfected cells with 8-bromo-cAMP increased expression directed by the 11.beta.-OHase 5''-flanking region by 3.8-fold. In 5''-deletion analyses, 123 base pairs of 5''-flanking sequences were sufficient for cAMP induction, whereas cAMP treatment did not affect expression of a plasmid with only 40 base pairs of 5''-flanking sequence. Within these 123 base pairs, a region from -56 to -49 matched 7 of 8 bases comprising the consensus sequence for the CRE. 11.beta.-OHase 5''-flanking sequences from -65 to -42, including the CRE-like sequence, conferred cAMP inducibility to promoters from the thymidine kinase and chorionic gonadotropin .alpha.-subunit genes. DNase I footprinting and Southwestern blotting analyses demonstrated that the protein which interacted with the CRE in the 11.beta.-OHase promoter region was similar to the CRE-binding protein associated with other cAMP-regulated genes. Together, these results suggest that an interaction between the 11.beta.-OHase CRE and CRE-binding protein mediates cAMP induction of the 11.beta.-OHase gene.

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