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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

12 Issues per year


IMPACT FACTOR 2017: 3.022

CiteScore 2017: 2.81

SCImago Journal Rank (SJR) 2017: 1.562
Source Normalized Impact per Paper (SNIP) 2017: 0.705

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1437-4315
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Volume 384, Issue 5

Issues

Trichostatin A and Structurally Related Histone Deacetylase Inhibitors Induce 5-Lipoxygenase Promoter Activity

N. Klan / S. Seuter / N. Schnur / M. Jung / D. Steinhilber
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/BC.2003.086

Abstract

5-Lipoxygenase (5-LO) mRNA expression in Mono Mac 6 cells is induced by the histone deacetylase inhibitor trichostatin A (TsA). In order to study the effects of TsA and several structurally related compounds such as MD85, D237 and M232 on 5-LO promoter activity, we have analyzed the response of a 5-lipoxygenase (5-LO) promoter luciferase reporter gene construct to histone deacetylase inhibitors in transiently transfected Mono Mac 6 and HeLa cells. We show that the activity of 5-LO promoter constructs comprising the sequences -778 to +53 and of several successive deletions of the 5-LO promoter is strongly increased upon TsA treatment. The data suggest a significant involvement of histone deacetylases in the regulation of 5-LO gene transcription. The basal activity of the 5-LO promoter strongly depends on the presence of multiple Sp1-binding sites (GC-boxes), five of which are positioned in tandem. Deletion of the five tandemized GCboxes in the 5-LO reporter gene construct revealed that the induction of 5-LO promoter activity by TsA seems to be independent of these GCboxes. Methylation of 5-LO reporter gene constructs by M.HpaII reduced 5-LO promoter activity but did not prevent induction of promoter activity by TsA, although the activated reporter gene activities were lower compared to the unmethylated plasmid, indicating the dominance of methylation over TsA-sensitive histone deacetylation in silencing of the 5-LO gene. The structure-activity data obtained for histone deacetylase inhibitors suggest that this assay system might serve as a cellular screening tool for the development of HDAC inhibitors.

About the article

Published Online: 2005-06-01

Published in Print: 2003-05-15


Citation Information: Biological Chemistry, Volume 384, Issue 5, Pages 777–785, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2003.086.

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