Location of the Repressor Site of Rat Hepatic Hydroxysteroid Sulfotransferase (SULT2-40/41)
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Authors
Ebenhoe, Emily L.
Issue Date
1999
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Understanding the molecular mechanisms that regulate the expression of the rat
hepatic hydroxysteroid sulfotransferase gene (SULT2-40/41) is important in
understanding its role in drug metabolism, carcinogen activation, bile acid detoxification
and regulation of intra-tissue active hormone levels. Glucocorticoids have been shown to induce SULT2-40/41 gene transcription. A recent study of the activating region has
pointed to an inhibiting region in the ~2000 bp 5' upstream promoting region of this
gene. The location of this inhibiting region was investigated by making several deletion
constructs of a previously made construct not containing the activating site (-227/-158).
The promoter region constructs ligated into luciferase reporter vectors were transiently
transfected into primary rat hepatocytes. Treatment with a synthetic glucocorticoid,
dexamethasone, induced gene transcription in all of the constructs. However, the
smallest construct, beginning 158 bp upstream (-158) from the transcription start site,
continued to have significantly higher SULT2-40/41 gene expression than any of the
other constructs. This implies that the repressor site is located within the next smallest
DNA construct, -268 from the transcription start site. Since this region does not contain
the -227/-158 activating region, the inhibiting region is therefore located in the -268/-227
region. This region has previously been studied in relation to androgen responsiveness,
and it is already known that there are three protein binding sites within this -268
5'-flanking region. With further study, it is likely that one of these three sites can be
implicated as the site that regulates the inhibition of SULT2-40/41 gene expression.
Description
iv, 30 p.
Citation
Publisher
Kalamazoo College
License
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