Open chromatin structure in PolyQ disease-related genes: a potential mechanism for CAG repeat expansion in the normal human population

Matan Sorek, Lea R.Z. Cohen, Eran Meshorer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageAmerican English
Article numberlqz003
JournalNAR Genomics and Bioinformatics
Volume1
Issue number1
DOIs
StatePublished - 1 Apr 2019

Bibliographical note

Publisher Copyright:
© The Author(s) 2019. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.

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