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Reorganization of inter-chromosomal interactions in the 2q37-deletion syndrome

Item Type:Article
Title:Reorganization of inter-chromosomal interactions in the 2q37-deletion syndrome
Creators Name:Maass, P.G. and Weise, A. and Rittscher, K. and Lichtenwald, J. and Barutcu, A.R. and Liehr, T. and Aydin, A. and Wefeld-Neuenfeld, Y. and Pölsler, L. and Tinschert, S. and Rinn, J.L. and Luft, F.C. and Bähring, S.
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.
Keywords:2q37-Deletion Syndrome, Mendelian Disease, Non-Homologous Chromosomal Contact, Non-Random Interphase Architecture, Nuclear Repositioning
Source:EMBO Journal
ISSN:0261-4189
Publisher:Wiley-Blackwell (U.S.A.)
Volume:37
Number:15
Page Range:e96257
Date:1 August 2018
Official Publication:https://doi.org/10.15252/embj.201696257
PubMed:View item in PubMed

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