Three-dimensional chromatin interactions remain stable upon CAG/CTG repeat expansion.
- Ruiz Buendía GA Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.
- Leleu M School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
- Marzetta F Vital-IT Group, Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
- Vanzan L Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland.
- Tan JY Department of Computational Biology, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.
- Ythier V Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland.
- Randall EL UK Dementia Research Institute at Cardiff University at Cardiff University, Hadyn Ellis Building, Maindy Road, CF24 4HQ Cardiff, UK.
- Marques AC Department of Computational Biology, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.
- Baubec T Department of Molecular Mechanisms of Disease, University of Zurich, 8057 Zurich, Switzerland.
- Murr R Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland.
- Xenarios I Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.
- Dion V UK Dementia Research Institute at Cardiff University at Cardiff University, Hadyn Ellis Building, Maindy Road, CF24 4HQ Cardiff, UK.
- 2020-07-14
Published in:
- Science advances. - 2020
English
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.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.1126/sciadv.aaz4012
- PMID 32656337
- Persistent URL
- https://sonar.ch/global/documents/50750
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