Three-dimensional chromatin interactions remain stable upon CAG/CTG repeat expansion.

Details

Serval ID
serval:BIB_E413F4743329
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Three-dimensional chromatin interactions remain stable upon CAG/CTG repeat expansion.
Journal
Science advances
Author(s)
Ruiz Buendía G.A., Leleu M., Marzetta F., Vanzan L., Tan J.Y., Ythier V., Randall E.L., Marques A.C., Baubec T., Murr R., Xenarios I., Dion V.
ISSN
2375-2548 (Electronic)
ISSN-L
2375-2548
Publication state
Published
Issued date
07/2020
Peer-reviewed
Oui
Volume
6
Number
27
Pages
eaaz4012
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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.
Pubmed
Web of science
Open Access
Yes
Create date
24/07/2020 10:26
Last modification date
14/10/2020 5:23
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