Chromatin changes induced by lamin A/C deficiency and the histone deacetylase inhibitor trichostatin A.
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 HP1beta 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 histones may play an important role in higher-order chromatin organization, which influences transcriptional activity.
Galiová
Gabriela
G
Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Královopolská 135, CZ-612 65 Brno, Czech Republic.
Bártová
Eva
E
Raska
Ivan
I
Krejcí
Jana
J
Kozubek
Stanislav
S
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002503:Centromere / Q000378:metabolism; D002843:Chromatin / Q000187:drug effects* / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects*; D000090266:Chromobox Protein Homolog 5; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism; D006570:Heterochromatin / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000494:pharmacology*; D034904:Lamin Type A / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D034921:Lamin Type B / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism
C000715593:CBX1 protein, human; D002843:Chromatin; D004791:Enzyme Inhibitors; D006570:Heterochromatin; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C494847:LMNA protein, human; D034904:Lamin Type A; D034921:Lamin Type B; D009687:Nuclear Proteins; D000090266:Chromobox Protein Homolog 5; C012589:trichostatin A