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

Cited 9 time in scopus
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Title
Age-associated chromatin relaxation is enhanced in Huntington's disease mice
Author(s)
M Park; B Min; K Jeon; S Cho; Jung Sun Park; J Kim; J Jeon; Jinhoi Song; Seok Ho Kim; S Jeong; H Seo; Yong-Kook Kang
Bibliographic Citation
Aging-Us, vol. 9, no. 3, pp. 803-822
Publication Year
2017
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.
Keyword
AgingChromatin accessibilityEpigeneticHuntingtin (HTT)Huntington's diseaseTargeted NGS
ISSN
1945-4589
Publisher
Impact Journals Llc
DOI
http://dx.doi.org/10.18632/aging.101193
Type
Article
Appears in Collections:
Division of Research on National Challenges > Aging Research Center > 1. Journal Articles
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