SUV39h- and A-type lamin-dependent telomere nuclear rearrangement.
Telomeres are specialized chromatin structures that are situated at the end of linear chromosomes and play an important role in cell senescence and immortalization. Here, we investigated whether changes in histone signature influence the nuclear arrangement and positioning of telomeres. Analysis of mouse embryonic fibroblasts revealed that telomeres were organized into specific clusters that partially associated with centromeric clusters. This nuclear arrangement was influenced by deficiency of the histone methyltransferase SUV39h, LMNA deficiency, and the histone deacetylase inhibitor Trichostatin A (TSA). Similarly, nuclear radial distributions of telomeric clusters were preferentially influenced by TSA, which caused relocation of telomeres closer to the nuclear center. Telomeres also co-localized with promyelocytic leukemia bodies (PML). This association was increased by SUV39h deficiency and decreased by LMNA deficiency. These differences could be explained by differing levels of the telomerase subunit, TERT, in SUV39h- and LMNA-deficient fibroblasts. Taken together, our data show that SUV39h and A-type lamins likely play a key role in telomere maintenance and telomere nuclear architecture.
Uhlírová
Radka
R
Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Královopolská 135, CZ-612 65 Brno, Czech Republic.
Horáková
Andrea Harnicarová
AH
Galiová
Gabriela
G
Legartová
Sona
S
Matula
Pavel
P
Fojtová
Miloslava
M
Varecha
Miroslav
M
Amrichová
Jana
J
Vondrácek
Jan
J
Kozubek
Stanislav
S
Bártová
Eva
E
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D015321:Gene Rearrangement; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism; D034904:Lamin Type A / Q000378:metabolism*; D008780:Methyltransferases / Q000378:metabolism*; D051379:Mice; D021381:Protein Transport; D012097:Repressor Proteins / Q000378:metabolism*; D000089804:Shelterin Complex; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism
D004268:DNA-Binding Proteins; D034904:Lamin Type A; C507326:POT1 protein, mouse; D012097:Repressor Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; C498700:Suv39h1 protein, mouse; D008780:Methyltransferases; D019098:Telomerase; D020827:rap1 GTP-Binding Proteins