Reorganization of inter‐ chromosomal interactions in the 2q37‐deletion syndrome
| العنوان: | Reorganization of inter‐ chromosomal interactions in the 2q37‐deletion syndrome |
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| المؤلفون: | A. Rasim Barutcu, Laura Pölsler, Yvette Wefeld-Neuenfeld, Philipp G. Maass, Atakan Aydin, Katharina Rittscher, Thomas Liehr, Julia Lichtenwald, Sigrid Tinschert, Sylvia Bähring, Anja Weise, Friedrich C. Luft, John L. Rinn |
| المساهمون: | Medical Genetics |
| المصدر: | The EMBO Journal. 37 |
| بيانات النشر: | EMBO, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Interphase/genetics, 0301 basic medicine, Cell type, Cell Nucleus/genetics, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Chromosomes, Human, Pair 17/genetics, medicine, Humans, Chromosomes, Human, Pair 2/genetics, Molecular Biology, In Situ Hybridization, Fluorescence, Chromosome 12, Genetics, Chromosomes, Human, Pair 12/genetics, Histone Deacetylases/genetics, Repressor Proteins/genetics, General Immunology and Microbiology, Mesenchymal Stem Cells/cytology, General Neuroscience, Mesenchymal stem cell, Chromosome, Karyotype, Translocation, Genetic/genetics, HDAC4, 030104 developmental biology, medicine.anatomical_structure, Interphase, Chromosome Deletion, Nucleus, Gene Deletion |
| الوصف: | 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. |
| تدمد: | 1460-2075 0261-4189 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::95b0d29c3b3acb595fda03dee414610fTest https://doi.org/10.15252/embj.201696257Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....95b0d29c3b3acb595fda03dee414610f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602075 02614189 |
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