상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

Age-associated chromatin relaxation is enhanced in Huntington's disease mice

Authors 

M ParkB MinK JeonS ChoJung Sun ParkJ KimJ JeonJinhoi SongSeok Ho KimS JeongH SeoYong-Kook Kang

Publisher 

Impact Journals

Issue Date 

2017

Citation 

Aging

Keywords 

AgingChromatin accessibilityEpigeneticHuntingtin (HTT)Huntington's diseaseTargeted NGS

Abstract 

Expansion of polyglutamine stretch in the huntingtin (HTT) protein is a major cause of Huntington's disease (HD). The polyglutamine part in HTT interacts with various proteins implicated in epigenetic regulation of genes, suggesting that mutant HTT may disturb the integrity of the epigenetic system. Here, we used a PCRseq-based method to examine expression profile of 395 exonic segments from 260 "epi-driver" genes in splenic T lymphocytes from aged HD mice. We identified 67 exonic segments differentially expressed between young and aged HD mice, most of them upregulated in the aged. Polycomb-repressive complex (PRC)-regulated genes (PRGs) were markedly upregulated in aged HD mice, consistent with downregulation of PRC genes. Epi-driver gene categories of lysine-methylation, lysine-demethylation, arginine-methylation, and PRG showed differential age-associated changes between HD and control. Analyzing the pattern of change in epi-driver gene expressions hinted at an enhanced shift in HD chromatin to a more accessible state with age, which was experimentally demonstrated by DNase-I-hypersensitivity sequencing showing increased chromatin accessibility in HD cells compared to control. We suggest the global change can potentially relieve chromatin-induced repression of many genes, and the unintended expressions of some detrimental proteins could alter T cell function to a greater degree in aged HD mice.

ISSN 

1945-4589

Link 

http://dx.doi.org/10.18632/aging.101193

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


Files in This Item: SizeFormat
14741.pdf1712KbAdobe PDF
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)