TY - JOUR
T1 - Open chromatin structure in PolyQ disease-related genes
T2 - a potential mechanism for CAG repeat expansion in the normal human population
AU - Sorek, Matan
AU - Cohen, Lea R.Z.
AU - Meshorer, Eran
N1 - Publisher Copyright: © The Author(s) 2019. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85101981280&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/nargab/lqz003
DO - https://doi.org/10.1093/nargab/lqz003
M3 - مقالة
SN - 2631-9268
VL - 1
JO - NAR Genomics and Bioinformatics
JF - NAR Genomics and Bioinformatics
IS - 1
M1 - lqz003
ER -