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@article{992777,
author = {Činčárová, Lenka and Lochmanová, Gabriela and Nováková, Kateřina and Šilerová, Pavla and Konečná, Hana and Fajkusová, Lenka and Fajkus, Jiří and Zdráhal, Zbyněk},
article_location = {Cambridge},
article_number = {11},
doi = {http://dx.doi.org/10.1039/c2mb25136a},
keywords = {histone acetylation; inhibitors of histone deacetylases; MALDI-MS; LC-MS/MS},
language = {eng},
issn = {1742-206X},
journal = {Molecular BioSystems},
title = {A combined approach for the study of histone deacetylase inhibitors},
url = {http://pubs.rsc.org/en/Content/ArticleLanding/2012/MB/c2mb25136a},
volume = {8},
year = {2012}
}
TY - JOUR
ID - 992777
AU - Činčárová, Lenka - Lochmanová, Gabriela - Nováková, Kateřina - Šilerová, Pavla - Konečná, Hana - Fajkusová, Lenka - Fajkus, Jiří - Zdráhal, Zbyněk
PY - 2012
TI - A combined approach for the study of histone deacetylase inhibitors
JF - Molecular BioSystems
VL - 8
IS - 11
SP - 2937-2945
EP - 2937-2945
PB - ROYAL SOC CHEMISTRY
SN - 1742206X
KW - histone acetylation
KW - inhibitors of histone deacetylases
KW - MALDI-MS
KW - LC-MS/MS
UR - http://pubs.rsc.org/en/Content/ArticleLanding/2012/MB/c2mb25136a
L2 - http://pubs.rsc.org/en/Content/ArticleLanding/2012/MB/c2mb25136a
N2 - Overexpression of histone deacetylases (HDACs), with consequent hypoacetylation of histones, is reportedly associated with transcriptional repression of tumour suppressor genes. Thus, inhibition of HDACs has emerged as a promising strategy in cancer therapy. In order to monitor the effects of potential HDAC inhibitors, a multi-level approach consisting of preliminary screening (measurement of HDAC activity and semi-quantitative evaluation of histone H4 modification profile by MALDI-TOF MS) and detailed analysis of histone modification forms (using 2-D AUT/AU PAGE and LC-ESI-IT MS) has been used in this study. The data obtained provide a global insight into the effects of HDAC inhibitors on the histone acetylation status that participates in gene transcription control. Using two example inhibitors, valproic acid sodium salt and entinostat, we show that similar levels of HDAC inhibition induced by different agents can lead to distinct rates of histone hyperacetylation, suggesting that except for the direct inhibition of HDACs, additional molecular mechanisms amplifying the response are likely to be involved in the inhibitory process. The approach used in our study makes it possible not only to follow the dynamics of individual histone modification forms, but also of their combined occurrence in the N-terminal fragment.
ER -
ČINČÁROVÁ, Lenka, Gabriela LOCHMANOVÁ, Kateřina NOVÁKOVÁ, Pavla ŠILEROVÁ, Hana KONEČNÁ, Lenka FAJKUSOVÁ, Jiří FAJKUS and Zbyněk ZDRÁHAL. A combined approach for the study of histone deacetylase inhibitors. \textit{Molecular BioSystems}. Cambridge: ROYAL SOC CHEMISTRY, 2012, vol.~8, No~11, p.~2937-2945. ISSN~1742-206X. doi:10.1039/c2mb25136a.
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