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Promoter Scanning for Transcription Inhibition with DNA-Binding Polyamides

Ehley, Jennifer A. and Melander, Christian and Herman, David and Baird, Eldon E. and Ferguson, Heather A. and Goodrich, James A. and Dervan, Peter B. and Gottesfeld, Joel M. (2002) Promoter Scanning for Transcription Inhibition with DNA-Binding Polyamides. Molecular and Cellular Biology, 22 (6). pp. 1723-1733. ISSN 0270-7306. PMCID PMC135605. https://resolver.caltech.edu/CaltechAUTHORS:EHLmcb02

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Abstract

When targeted to sequences adjacent to a TATA element, pyrrole-imidazole (Py-Im) polyamides inhibit the DNA binding activity of TATA box binding protein (TBP) and basal transcription by RNA polymerase II. In the present study, we scanned the human immunodeficiency virus type 1 promoter for polyamide inhibition of TBP binding and transcription using a series of DNA constructs in which a polyamide binding site was placed at various distances from the TATA box. Polyamide interference with either TBP-DNA or TFIID-TFIIA-DNA contacts both upstream and downstream of the TATA element resulted in inhibition of transcription. Our results define important protein-DNA interactions outside of the TATA element and suggest that transcription inhibition of selected gene promoters can be achieved with polyamides that target unique sequences within these promoters at a distance from the TATA element. Our studies also demonstrate the utility of the Py-Im polyamides for discovery of functionally important protein-DNA contacts involved in transcription.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC135605/PubMed CentralArticle
https://doi.org/10.1128/MCB.22.6.1723-1733.2002DOIUNSPECIFIED
https://doi.org/10.1128/MCB.22.6.1723-1733.2002DOIUNSPECIFIED
ORCID:
AuthorORCID
Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 2002 American Society for Microbiology. Received 13 August 2001/ Returned for modification 1 October 2001/ Accepted 29 October 2001 We thank Tae-Kyung Kim and D. Reinberg for the generous gift of TFIIA and Liliane Dickinson and E. Peter Geiduschek for discussions. This work was supported by National Institutes of Health grants GM57148 to J.M.G. and P.B.D. and GM55235 to J.A.G. The Howard Hughes Medical Institute provided a predoctoral fellowship for E.E.B., and C.M. was supported by a postdoctoral fellowship from the NIH (GM19789).
Funders:
Funding AgencyGrant Number
NIHGM-57148
NIHGM-55235
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIH Postdoctoral FellowshipGM-19789
Issue or Number:6
PubMed Central ID:PMC135605
Record Number:CaltechAUTHORS:EHLmcb02
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:EHLmcb02
Official Citation:Promoter Scanning for Transcription Inhibition with DNA-Binding Polyamides Jennifer A. Ehley, Christian Melander, David Herman, Eldon E. Baird, Heather A. Ferguson, James A. Goodrich, Peter B. Dervan, and Joel M. Gottesfeld Mol. Cell. Biol. March 2002 22:6 1723-1733; doi:10.1128/MCB.22.6.1723-1733.2002
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:2409
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:03 Apr 2006
Last Modified:26 Nov 2019 11:15

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