Three-dimensional chromatin interactions remain stable upon CAG/CTG repeat expansion
| Autor: | Tuncay Baubec, Ana C. Marques, Gustavo A. Ruiz Buendía, Flavia Marzetta, Marion Leleu, Ludovica Vanzan, Ioannis Xenarios, Victor Ythier, Rabih Murr, Vincent Dion, Emma L. Randall, Jennifer Y. Tan |
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| Přispěvatelé: | University of Zurich, Dion, Vincent |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
musculoskeletal diseases
congenital hereditary and neonatal diseases and abnormalities binding Heterochromatin friedreichs-ataxia Biology Myotonic dystrophy fmr1 03 medical and health sciences 0302 clinical medicine medicine Genetics read alignment Allele gene skin and connective tissue diseases Gene Research Articles 030304 developmental biology 0303 health sciences 1000 Multidisciplinary Multidisciplinary histone modifications epigenetic changes SciAdv r-articles medicine.disease FMR1 10226 Department of Molecular Mechanisms of Disease Chromatin nervous system diseases instability Histone Cellular Neuroscience DNA methylation cgg repeat biology.protein 570 Life sciences biology methylation sense organs 030217 neurology & neurosurgery Research Article |
| Zdroj: | Science Advances Science advances, vol. 6, no. 27, pp. eaaz4012 |
| ISSN: | 2375-2548 |
| Popis: | Unexpectedly, the molecular pathogenesis of expanded CAG/CTG diseases does not include changes in 3D chromatin conformation. Expanded CAG/CTG repeats underlie 13 neurological disorders, including myotonic dystrophy type 1 (DM1) and Huntington’s disease (HD). Upon expansion, disease loci acquire heterochromatic characteristics, which may provoke changes to chromatin conformation and thereby affect both gene expression and repeat instability. Here, we tested this hypothesis by performing 4C sequencing at the DMPK and HTT loci from DM1 and HD–derived cells. We find that allele sizes ranging from 15 to 1700 repeats displayed similar chromatin interaction profiles. This was true for both loci and for alleles with different DNA methylation levels and CTCF binding. Moreover, the ectopic insertion of an expanded CAG repeat tract did not change the conformation of the surrounding chromatin. We conclude that CAG/CTG repeat expansions are not enough to alter chromatin conformation in cis. Therefore, it is unlikely that changes in chromatin interactions drive repeat instability or changes in gene expression in these disorders. |
| Databáze: | OpenAIRE |
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