Doctoral Dissertations

Date of Award

5-1993

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Life Sciences

Major Professor

John Koontz

Committee Members

Mary Ann Handel, John M. Bezelle

Abstract

cis-acting DNA regions which mediate the transcriptional effects of insulin show little similarity among insulin-regulated genes. This study, using mutant promoter constructs transiently transfected into the KRC-7 rat hepatoma cell line, identified an insulin-responsive element (IRE) in the promoter of the gene encoding tyrosine aminotransferase (TAT). This IRE is required for insulin inhibition of both basal and cAMP-responsive transcription, and is located near a basal enhancer (BE) required for full basal expression and cAMP sensitivity. It is also distinct from a more proximal region required for insulin inhibition of glucocorticoid-induced transcription. In addition, the sufficiency of the BE for basal transcription was examined. A proximal TAT promoter region not essential for glucocorticoid-induced expression was found to be required for mediation of the BE's effect.

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