| Autor: |
Zhegalova IV; Center for Molecular and Cellular Biology, Skolkovo Institute of Science and Technology, 143026 Moscow, Russia.; A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, 127051 Moscow, Russia., Vasiluev PA; Research Centre for Medical Genetics, 115522 Moscow, Russia., Flyamer IM; Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland., Shtompel AS; Department of Molecular Biology, Faculty of Biology, M.V. Lomonosov Moscow State University, 119234 Moscow, Russia.; Laboratory of Structural-Functional Organization of Chromosomes, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia., Glazyrina E; Medical Genetic Center LLC Progen, 117630 Moscow, Russia., Shilova N; Research Centre for Medical Genetics, 115522 Moscow, Russia., Minzhenkova M; Research Centre for Medical Genetics, 115522 Moscow, Russia., Markova Z; Research Centre for Medical Genetics, 115522 Moscow, Russia., Petrova NV; Laboratory of Structural-Functional Organization of Chromosomes, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia., Dashinimaev EB; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, 117997 Moscow, Russia., Razin SV; Department of Molecular Biology, Faculty of Biology, M.V. Lomonosov Moscow State University, 119234 Moscow, Russia.; Laboratory of Structural-Functional Organization of Chromosomes, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia., Ulianov SV; Department of Molecular Biology, Faculty of Biology, M.V. Lomonosov Moscow State University, 119234 Moscow, Russia.; Laboratory of Structural-Functional Organization of Chromosomes, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia. |
| Abstrakt: |
Trisomy is the presence of one extra copy of an entire chromosome or its part in a cell nucleus. In humans, autosomal trisomies are associated with severe developmental abnormalities leading to embryonic lethality, miscarriage or pronounced deviations of various organs and systems at birth. Trisomies are characterized by alterations in gene expression level, not exclusively on the trisomic chromosome, but throughout the genome. Here, we applied the high-throughput chromosome conformation capture technique (Hi-C) to study chromatin 3D structure in human chorion cells carrying either additional chromosome 13 (Patau syndrome) or chromosome 16 and in cultured fibroblasts with extra chromosome 18 (Edwards syndrome). The presence of extra chromosomes results in systematic changes of contact frequencies between small and large chromosomes. Analyzing the behavior of individual chromosomes, we found that a limited number of chromosomes change their contact patterns stochastically in trisomic cells and that it could be associated with lamina-associated domains (LAD) and gene content. For trisomy 13 and 18, but not for trisomy 16, the proportion of compacted loci on a chromosome is correlated with LAD content. We also found that regions of the genome that become more compact in trisomic cells are enriched in housekeeping genes, indicating a possible decrease in chromatin accessibility and transcription level of these genes. These results provide a framework for understanding the mechanisms of pan-genome transcription dysregulation in trisomies in the context of chromatin spatial organization. |
