PT  - JOURNAL ARTICLE
AU  - Gustavo A. Ruiz Buendía
AU  - Marion Leleu
AU  - Flavia Marzetta
AU  - Ludovica Vanzan
AU  - Jennifer Y. Tan
AU  - Ana C. Marques
AU  - Tuncay Baubec
AU  - Rabih Murr
AU  - Ioannis Xenarios
AU  - Vincent Dion
TI  - Three-dimensional chromatin interactions remain stable upon CAG/CTG repeat expansion
AID  - 10.1101/754838
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 754838
4099  - http://biorxiv.org/content/early/2019/09/02/754838.short
4100  - http://biorxiv.org/content/early/2019/09/02/754838.full
AB  - Expanded CAG/CTG repeats underlie thirteen neurological disorders, including myotonic dystrophy (DM1) and Huntington’s disease (HD). Upon expansion, CAG/CTG repeat loci acquire heterochromatic characteristics. This observation raises the hypothesis that repeat expansion provokes changes to higher order chromatin folding and thereby affects both gene expression in cis and the genetic instability of the repeat tract. Here we tested this hypothesis directly by performing 4C sequencing at the DMPK and HTT loci from DM1 and HD patient-derived cells. Surprisingly, chromatin contacts remain unchanged upon repeat expansion at both loci. This was true for loci with different DNA methylation levels and CTCF binding. Repeat sizes ranging from 15 to 1,700 displayed strikingly similar chromatin interaction profiles. Our findings argue that extensive changes in heterochromatic properties are not enough to alter chromatin folding at expanded CAG/CTG repeat loci. Moreover, the ectopic insertion of an expanded repeat tract did not change three-dimensional chromatin contacts. We conclude that expanded CAG/CTG repeats have little to no effect on chromatin conformation.