Abstracts (poster) - Wissenschaft Online

Careen Katryniok, Bernd L. Sorg, Dieter Steinhilber
INDUCTION OF HUMAN 5-LIPOXYGENASE GENE EXPRESSION
BY THE HISTONE DEACETYLASE INHIBITOR TRICHOSTATIN A -
INVESTIGATIONS ON THE MECHANISM
5-lipoxygenase (5-LO) is the key enzyme in the formation of leukotrienes which are
important inflammatory mediators. The 5-LO promoter lacks a TATA or CCAT box, but
posseses a unique GC-rich sequence (1). We have shown previously that epigenetic
mechanisms play a role in the transcription of 5-lipoxygenase. The 5-LO transcription is
silenced by DNA methylation (2,3) and activated by treatment with histone desacetylase
inhibitior trichostatin A (TsA) (4).
In this study, we continued the investigations concerning the activation of the 5-LO
promoter by TsA. We explored the time dependency of the effect of TsA by rt-PCR and
achieved the maximal effect 8-16 hours after incubation. Subsequently we analysed
changes in the histone modifications of three different cell lines after TsA incubation, two
of which are transcriptionally active (HL-60 and MM6 cells), whereas the third cell line is
methylated and silenced (U937). We could discover differences between this cell lines in
the acetylation pattern of the core histone proteins H3 and H4 using the chromatin
immunoprecipitation assay. In TsA treated HL-60 and, surprisingly in U937 cells, we
could detect an increase of acetylated Histon H3 and H4 with a maximum after 8-16
hours. Interestingly, no change in histone acetylation status is seen in the cell line MM6.
It looks as if TsA does not act via the classical mechanism, which is increase of
acetylation state of histone proteins, in MM6 cells.
Literature
1. Hoshiko, S., Rådmark, O., and Samuelsson, B. (1990) Proceedings of the National
Academy of Sciences of the United States of America 87, 9073-9077
2. Uhl, J., Klan, N., Rose, M., Entian, K. D., Werz, O., and Steinhilber, D. (2002) Journal
of Biological Chemistry 277, 4374-4379
3. Uhl, J., Klan, N., Rose, M., Entian, K. D., Werz, O., and Steinhilber, D. (2003)
Advances in Experimental Medicine & Biology 525, 169-172
4. Klan, N., Seuter, S., Schnur, N., Jung, M., and Steinhilber, D. (2003) Biological
Chemistry 384, 777-785
contact:
Careen Katryniok
University of Frankfurt
Institute of Pharmaceutical Chemistry
Katryniok@pharmchem.uni-frankfurt.de
Max-von-Laue-Str. 9
60438 Frankfurt (Germany)