Reorganization of inter-chromosomal interactions in the 2q37-deletion syndrome.
EMBO J
; 37(15)2018 08 01.
Article
em En
| MEDLINE
| ID: mdl-29921581
ABSTRACT
Chromosomes occupy distinct interphase territories in the three-dimensional nucleus. However, how these chromosome territories are arranged relative to one another is poorly understood. Here, we investigated the inter-chromosomal interactions between chromosomes 2q, 12, and 17 in human mesenchymal stem cells (MSCs) and MSC-derived cell types by DNA-FISH We compared our findings in normal karyotypes with a three-generation family harboring a 2q37-deletion syndrome, featuring a heterozygous partial deletion of histone deacetylase 4 (HDAC4) on chr2q37. In normal karyotypes, we detected stable, recurring arrangements and interactions between the three chromosomal territories with a tissue-specific interaction bias at certain loci. These inter-chromosomal interactions were confirmed by Hi-C. Interestingly, the disease-related HDAC4 deletion resulted in displaced inter-chromosomal arrangements and altered interactions between the deletion-affected chromosome 2 and chromosome 12 and/or 17 in 2q37-deletion syndrome patients. Our findings provide evidence for a direct link between a structural chromosomal aberration and altered interphase architecture that results in a nuclear configuration, supporting a possible molecular pathogenesis.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Translocação Genética
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Cromossomos Humanos Par 2
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Cromossomos Humanos Par 12
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Cromossomos Humanos Par 17
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Deleção de Genes
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Histona Desacetilases
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article