XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
42.
HISTONE aCETYLaTION of LEUKEMIC Jurl-MK1 CELLS WITHIN SAHA
treaTMENT
Michaela Pluskalová, Dana Grebeňová, Zbyněk Hrkal and Kateřina Kuželová
Institute of Hematology and Blood Transfusion, Prague, Czech Republic
The basic unit of chromatin, the nucleosome, is formed by about 146 bp of DNA wrapped
around the histone octamer. The histones play an important role in the arrangement of
nucleosomes. N-terminal tails of histones undergo multiple reversible posttranslational
modifications, which have been proposed to form the so-called ´histone code´. This code
(epigenetic information) regulates the binding of transcription complexes and determines
gene transcription rate. The best understood histone modification is the lysine acetylation
which occurs as a result of mutually opposed activities of histone acetyltransferases
(HAT) and histone deacetylases (HDAC).
Suberoylanilide hydroxamic acid (SAHA) is the first member of the group of HDAC inhibitors
which is used for treating patients with cutaneous T-cell lymphoma. While it is
also evaluated in clinical trials for the treatment of other oncological and hematological
diseases, the mechanism of its action is largely unexplained. We found that the effect
of SAHA on the leukemic cell line JURL-MK1 are strongly dose-dependent: an increase
in the cellular adhesivity to fibronectin and cell cycle arrest was observed for subtoxic
SAHA concentration while the apoptosis was triggered at higher doses. Using specific
antibodies against the individual acetylation sites, we identified dose-dependent changes
in the acetylation of histones H2A, H2B and H4 induced by SAHA treatment. We also
detected changes in the cellular localization of these histones (transfer from nuclear to
cytoplasmic fraction) due to SAHA.
Acknowledgement: This work was supported by grant 301/09/1026 from the Grant
Agency of the Czech Republic.
160 XXII. Biochemistry Congress, Martin