Cohesinopathy mutations disrupt the subnuclear organization of chromatin.
J Cell Biol
; 187(4): 455-62, 2009 Nov 16.
Article
em En
| MEDLINE
| ID: mdl-19948494
ABSTRACT
In Saccharomyces cerevisiae, chromatin is spatially organized within the nucleus with centromeres clustering near the spindle pole body, telomeres clustering into foci at the nuclear periphery, ribosomal DNA repeats localizing within a single nucleolus, and transfer RNA (tRNA) genes present in an adjacent cluster. [corrected] Furthermore, certain genes relocalize from the nuclear interior to the periphery upon transcriptional activation. The molecular mechanisms responsible for the organization of the genome are not well understood. We find that evolutionarily conserved proteins in the cohesin network play an important role in the subnuclear organization of chromatin. Mutations that cause human cohesinopathies had little effect on chromosome cohesion, centromere clustering, or viability when expressed in yeast. However, two mutations in particular lead to defects in (a) GAL2 transcription and recruitment to the nuclear periphery, (b) condensation of mitotic chromosomes, (c) nucleolar morphology, and (d) tRNA gene-mediated silencing and clustering of tRNA genes. We propose that the cohesin network affects gene regulation by facilitating the subnuclear organization of chromatin.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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Acetiltransferases
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Proteínas Nucleares
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Cromatina
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Proteínas Cromossômicas não Histona
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Núcleo Celular
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Proteínas de Ciclo Celular
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Proteínas de Saccharomyces cerevisiae
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article