Open chromatin structure in PolyQ disease-related genes: a potential mechanism for CAG repeat expansion in the normal human population.
Journal
NAR genomics and bioinformatics
ISSN: 2631-9268
Titre abrégé: NAR Genom Bioinform
Pays: England
ID NLM: 101756213
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
17
05
2019
revised:
07
07
2019
accepted:
16
07
2019
entrez:
12
2
2021
pubmed:
30
7
2019
medline:
30
7
2019
Statut:
epublish
Résumé
The human genome contains dozens of genes that encode for proteins containing long poly-glutamine repeats (polyQ, usually encoded by CAG codons) of 10Qs or more. However, only nine of these genes have been reported to expand beyond the healthy variation and cause diseases. To address whether these nine disease-associated genes are unique in any way, we compared genetic and epigenetic features relative to other types of genes, especially repeat containing genes that do not cause diseases. Our analyses show that in pluripotent cells, the nine polyQ disease-related genes are characterized by an open chromatin profile, enriched for active chromatin marks and depleted for suppressive chromatin marks. By contrast, genes that encode for polyQ-containing proteins that are not associated with diseases, and other repeat containing genes, possess a suppressive chromatin environment. We propose that the active epigenetic landscape support decreased genomic stability and higher susceptibility for expansion mutations.
Identifiants
pubmed: 33575550
doi: 10.1093/nargab/lqz003
pii: lqz003
pmc: PMC7671342
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e3Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.
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