We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
3D-FISH analysis reveals chromatid cohesion defect during interphase in Roberts syndrome.
- Authors
Dupont, Celine; Bucourt, Martine; Guimiot, Fabien; Kraoua, Lilia; Smiljkovski, Daniel; Le Tessier, Dominique; Lebugle, Camille; Gerard, Benedicte; Spaggiari, Emmanuel; Bourdoncle, Pierre; Tabet, Anne-Claude; Benzacken, Brigitte; Dupont, Jean-Michel
- Abstract
Background Roberts syndrome (RBS) is a rare autosomal recessive disorder mainly characterized by growth retardation, limb defects and craniofacial anomalies. Characteristic cytogenetic findings are "railroad track" appearance of chromatids and premature centromere separation in metaphase spreads. Mutations in the ESCO2 (establishment of cohesion 1 homolog 2) gene located in 8p21.1 have been found in several families. ESCO2, a member of the cohesion establishing complex, has a role in the effective cohesion between sister chromatids. In order to analyze sister chromatids topography during interphase, we performed 3D-FISH using pericentromeric heterochromatin probes of chromosomes 1, 4, 9 and 16, on preserved nuclei from a fetus with RBS carrying compound heterozygous null mutations in the ESCO2 gene. Results Along with the first observation of an abnormal separation between sister chromatids in heterochromatic regions, we observed a statistically significant change in the intranuclear localization of pericentromeric heterochromatin of chromosome 1 in cells of the fetus compared to normal cells, demonstrating for the first time a modification in the spatial arrangement of chromosome domains during interphase. Conclusion We hypothesize that the disorganization of nuclear architecture may result in multiple gene deregulations, either through disruption of DNA cis interaction -such as modification of chromatin loop formation and gene insulation - mediated by cohesin complex, or by relocation of chromosome territories. These changes may modify interactions between the chromatin and the proteins associated with the inner nuclear membrane or the pore complexes. This model offers a link between the molecular defect in cohesion and the complex phenotypic anomalies observed in RBS.
- Subjects
ROBERTS syndrome; MATERIAL plasticity; INTERPHASE; CELL cycle; GENETIC disorders
- Publication
Molecular Cytogenetics (17558166), 2014, Vol 7, Issue 1, p1
- ISSN
1755-8166
- Publication type
Article
- DOI
10.1186/s13039-014-0059-6