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Modulation of Sp1-dependent transcription by a cis-acting E2F element in dhfr promoter

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Author(s)
박관규김현철이인규
Alternative Author(s)
Park, Kwan KyuKim, Hyun ChulLee, In Kyu
Publication Year
2003
Abstract
The dihydrofolate reductase (dhfr) promoter contains cis-acting elements for Sp1 and E2F. Here we examined the cooperative
regulation of dhfr gene transcription by Sp1 and E2F in human osteosarcoma cells, U2OS. Trichostatin A, an inhibitor of histone
deacetylases, markedly stimulated dhfr promoter activity, a response that was enhanced by the deletion of an E2F element. In
contrast, deletion of the dhfr Sp1 binding sites completely abolished promoter stimulation by trichostatin A. Cotransfection assays
showed that activation of dhfr transcription by expression of E2F1/DP1 requires the reiterated Sp1 elements, whereas activation by
Sp1 was enhanced by the deletion of the E2F element. Expression of HDAC1 with Sp1 suppressed promoter activity and suppression
was not alleviated by coexpression of E2F1/DP1. These results suggest that HDAC1 acts through Sp1 to repress dhfr
promoter activity, and that the E2F element modulates the activity of Sp1 at the dhfr promoter through a cis-acting mechanism.
2003 Elsevier Science (USA). All rights reserved.
Keywords: Dihydrofolate reductase; Sp1; E2F; HDAC; Transcriptional repression
Department
Dept. of Internal Medicine (내과학)
Dept. of Pathology (병리학)
Kidney Institute (신장연구소)
Publisher
School of Medicine
Citation
Biochemical and Biophysical Research Communications, Vol.306(1) : 239-243, 2003
Type
Article
ISSN
0006-291X
DOI
10.1016/S0006-291X(03)00941-0
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35146
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