TY  - JOUR
A1  - Pufahl, Laura
A1  - Katryniok, Careen
A1  - Schnur, Nicole
A1  - Sorg, Bernd Lothar
A1  - Metzner, Julia
A1  - Grez, Manuel
A1  - Steinhilber, Dieter
T1  - Trichostatin A induces 5-lipoxygenase promoter activity and mRNA expression via inhibition of histone deacetylase 2 and 3
T2  - Journal of cellular and molecular medicine
N2  - The 5-lipoxygenase (5-LO) is the key enzyme in the formation of leukotrienes. We have previously shown that the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) activates 5-LO transcription via recruitment of Sp1, Sp3 and RNA polymerase II to the proximal promoter. To identify the HDACs involved in the regulation of 5-LO promoter activity isoform-specific HDAC inhibitors were applied. 5-LO promoter activity and mRNA expression were up-regulated by the class I HDAC inhibitors apicidin and MS-275 but not by class II inhibitors. Knockdown of HDAC 1, 2 and 3 revealed that HDAC2 and HDAC3 but not HDAC1 is involved in the up-regulation of 5-LO mRNA expression. To analyse the chromatin modifications at the 5-LO promoter associated with HDAC inhibition, the time course of 5-LO mRNA induction by trichostatin A was investigated and the concomitant changes in histone modifications at the 5-LO promoter in HL-60, U937 and Mono Mac6 cells were determined. Chromatin immunoprecipitation analysis revealed that trichostatin A increases acetylation of histones H3 and H4 at the 5-LO core promoter in HL-60 and U937 cells whereas no significant changes were observed in Mono Mac6 cells. The appearance of H3 and H4 acetylation preceded the 5-LO mRNA induction whereas in all three cell lines, induction of 5-LO mRNA expression correlated with histone H3 lysine 4 trimethylation (H3K4me3), a marker for transcriptional activity of gene promoters.
KW  - 5-lipoxygenase
KW  - epigenetics
KW  - histone deacetylase inhibitor
KW  - trichostatin A
KW  - chromatin immunoprecipitation
KW  - histone acetylation
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27962
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-279624
UR  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823215/
SN  - 1582-4934
SN  - 1582-1838
N1  - © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an Open Access article under the terms of the Creative Commons Attribution Non Commercial License http://creativecommons.org/licenses/by-nc/3.0/ which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
VL  - 16
IS  - 7
SP  - 1461
EP  - 1473
PB  - Wiley-Blackwell
CY  - Hoboken, NJ
ER  -