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


  • P.G. Maass
  • A. Weise
  • K. Rittscher
  • J. Lichtenwald
  • A.R. Barutcu
  • T. Liehr
  • A. Aydin
  • Y. Wefeld-Neuenfeld
  • L. Pölsler
  • S. Tinschert
  • J.L. Rinn
  • F.C. Luft
  • S. Bähring


  • EMBO Journal


  • EMBO J 37 (15): e96257


  • 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.