CHARACTERIZATION OF A NEGATIVE CIS-ACTING DNA ELEMENT REGULATING THE TRANSCRIPTION OF CYP2B1 B2 GENE IN RAT-LIVER/

The region -160 to -127 nt of the upstream of CYP-2B1/B2 gene has been found to function as a negative cis-acting element on the basis of DN ase-I footprint and gel mobility shift assays as well as cell-free tra nscriptional assays using Bal-31 mutants. A reciprocal relationship in the interaction of the negative and the recently characterized positi ve elements with their respective protein factors has been found under repressed and induced conditions of the gene. The negative element al so harbors the core glucocorticoid responsive sequence, TGTCCT. It is concluded that the negative element mediates the repressed state of th e gene under the uninduced condition and also mediates the repressive effect of dexamethasone, when given along with the inducer phenobarbit one in rats. Dexamethasone is able to antagonize the effects of phenob arbitone at as low a concentration as 100 mu g/kg body wt in these ani mals. (C) 1995 Academic Press,Inc.