Chromatin changes induced by lamin A/C deficiency and the histone deacetylase inhibitor trichostatin A

被引:61
作者
Galiova, Gabriela [1 ]
Bartova, Eva [1 ]
Raska, Ivan [2 ,3 ]
Krejci, Jana [1 ]
Kozubek, Stanislav [1 ]
机构
[1] Acad Sci Czech Republ, Inst Biophys, CZ-61265 Brno, Czech Republic
[2] Charles Univ Prague, Fac Med 1, Inst Cellular Biol & Pathol, CR-11636 Prague 1, Czech Republic
[3] Acad Sci Czech Republ, Inst Physiol, Dept Cell Biol, Brno, Czech Republic
关键词
lamin A/C; chromatin; HDAC inhibition; epigenetics;
D O I
10.1016/j.ejcb.2008.01.013
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Recent studies have shown that histone code dictates the type and structure of chromatin. Bearing in mind the importance of A-type lamins for chromatin arrangement, we studied the effect of trichostatin A (TSA)-induced histone hyperacetylation in lamin A/C-deficient (LMNA-/-) fibroblasts. Lamin A/C deficiency caused condensation of chromosome territories and the nuclear reorganization of centromeric heterochromatin, which was accompanied by the appearance of a chain-like morphology of HP1 beta foci. Conversely, histone deacetylase (HDAC) inhibition induced de-condensation of chromosome territories, which compensated the effect of lamin A/C deficiency on chromosome regions. The amount of heterochromatin in the area associated with the nuclear membrane was significantly reduced in LMNA-/- cells when compared with lamin A/C-positive (LMNA + / +) fibroblasts. TSA also decreased the amount of peripheral heterochromatin, similarly as lamin A/C deficiency. In both LMNA+/+ and LMNA-/- cells, physically larger chromosomes were positioned more peripherally as compared with the smaller ones, even after TSA treatment. Our observations indicate that lamin A/C deficiency causes not only reorganization of chromatin and some chromatin-associated domains, but also has an impact on the extent of chromosome condensation. As HDAC inhibition can compensate the lamin A/C-dependent chromatin changes, the interaction between lamins and specifically modified histories may play an important role in higher-order chromatin organization, which influences transcriptional activity. (C) 2008 Elsevier GmbH. All rights reserved.
引用
收藏
页码:291 / 303
页数:13
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