Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Isolation of the UDP-Glucuronosyltransferase 1A3 and 1A4 Proximal Promoters and Characterization of Their Dependence on the Transcription Factor Hepatocyte Nuclear Factor 1α

Dione A. Gardner-Stephen and Peter I. Mackenzie
Drug Metabolism and Disposition January 2007, 35 (1) 116-120; DOI: https://doi.org/10.1124/dmd.106.012203
Dione A. Gardner-Stephen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter I. Mackenzie
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

The UGT1A3-1A5 genes are a highly related UDP-glucuronosyltransferase (UGT) cluster exhibiting high levels of coding and regulatory region homology. However, the ensuing proteins have both differing substrate specificities and differing expression patterns. The expression profile of each enzyme also varies considerably from one individual to the next. Differences in UGT expression have been predicted to contribute to an individual's response to pharmaceuticals and to predisposition toward cancer in the event of carcinogen exposure. Therefore, it is desirable to elucidate the mechanisms that drive the transcription of UGT genes and identify the factors responsible for their variable expression. To this end, we have isolated the UGT1A3, UGT1A4, and UGT1A5 proximal promoters and begun to investigate the regulatory elements necessary for activity in vitro. We have established that the nucleotide sequence upstream of the UGT1A5 exon 1 is an ineffective promoter, correlating with the lack of substantial expression of this UGT in human tissues. In contrast, the UGT1A3 and UGT1A4 proximal promoters are both highly active in hepatic and colonic cell lines, with maximal activity being encoded by the proximal 500 base pairs. However, the UGT1A3 and UGT1A4 promoters exhibit low activity in the human embryonic kidney cell line HEK293, unless coexpressed with hepatocyte nuclear factor (HNF) 1α. Furthermore, mutation of the consensus-like HNF1-binding site in the UGT1A3 promoter abolishes promoter function in all cell types. This study suggests an important role for HNF1α in the transcriptional regulation of the human UGT1A3 and UGT1A4 genes.

Footnotes

  • This work was supported by grants from the Cancer Council of South Australia and the National Health and Medical Research Council of Australia. P.I.M. is a National Health and Medical Research Council Senior Principal Research Fellow.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.106.012203.

  • ABBREVIATIONS: UGT, UDP-glucuronosyltransferase; PCR, polymerase chain reaction; bp, base pair(s); HNF, hepatocyte nuclear factor; EMSA, electrophoretic mobility shift assay; FXR, farnesoid X receptor.

    • Received August 2, 2006.
    • Accepted October 17, 2006.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 35 (1)
Drug Metabolism and Disposition
Vol. 35, Issue 1
1 Jan 2007
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Isolation of the UDP-Glucuronosyltransferase 1A3 and 1A4 Proximal Promoters and Characterization of Their Dependence on the Transcription Factor Hepatocyte Nuclear Factor 1α
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Isolation of the UDP-Glucuronosyltransferase 1A3 and 1A4 Proximal Promoters and Characterization of Their Dependence on the Transcription Factor Hepatocyte Nuclear Factor 1α

Dione A. Gardner-Stephen and Peter I. Mackenzie
Drug Metabolism and Disposition January 1, 2007, 35 (1) 116-120; DOI: https://doi.org/10.1124/dmd.106.012203

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Isolation of the UDP-Glucuronosyltransferase 1A3 and 1A4 Proximal Promoters and Characterization of Their Dependence on the Transcription Factor Hepatocyte Nuclear Factor 1α

Dione A. Gardner-Stephen and Peter I. Mackenzie
Drug Metabolism and Disposition January 1, 2007, 35 (1) 116-120; DOI: https://doi.org/10.1124/dmd.106.012203
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results and Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Endogenous substrates of rat organic cation transporters
  • Catabolism and Metabolism of ABBV-011, a Calicheamicin ADC
  • Gadoxetate-enhanced MRI and FXR in benign tumours
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics