title: Age-associated chromatin relaxation is enhanced in Huntington's disease mice.
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.
authors.affiliation: Development and Differentiation Research Center, KRIBB, Yuseong-gu, Daejeon, 305-806, South Korea.
authors.forename: Myungsun
authors.initials: M
authors.lastname: Park
authors.affiliation: Development and Differentiation Research Center, KRIBB, Yuseong-gu, Daejeon, 305-806, South Korea.
authors.forename: Byungkuk
authors.initials: B
authors.lastname: Min
authors.affiliation: Development and Differentiation Research Center, KRIBB, Yuseong-gu, Daejeon, 305-806, South Korea.|Department of Functional Genomics, University of Science and Technology (UST), Yuseong-gu, Daejeon, 305-350, South Korea.
authors.forename: Kyuheum
authors.initials: K
authors.lastname: Jeon
authors.affiliation: Development and Differentiation Research Center, KRIBB, Yuseong-gu, Daejeon, 305-806, South Korea.
authors.forename: Sunwha
authors.initials: S
authors.lastname: Cho
authors.affiliation: Development and Differentiation Research Center, KRIBB, Yuseong-gu, Daejeon, 305-806, South Korea.|Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, South Korea.
authors.forename: Jung Sun
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Molecular and Life Sciences, Hanyang University, Sangnok-gu, Ansan, Gyeonggi-do, 15588, South Korea.
authors.forename: Jisun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Molecular and Life Sciences, Hanyang University, Sangnok-gu, Ansan, Gyeonggi-do, 15588, South Korea.
authors.forename: Jeha
authors.initials: J
authors.lastname: Jeon
authors.affiliation: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, South Korea.
authors.forename: Jinhoi
authors.initials: J
authors.lastname: Song
authors.affiliation: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, South Korea.
authors.forename: Seokho
authors.initials: S
authors.lastname: Kim
authors.affiliation: Mibyeong Research Center, Korea Institute of Oriental Medicine (KIOM), Yuseong-gu, Daejeon, 305-811, South Korea.
authors.forename: Sangkyun
authors.initials: S
authors.lastname: Jeong
authors.affiliation: Department of Molecular and Life Sciences, Hanyang University, Sangnok-gu, Ansan, Gyeonggi-do, 15588, South Korea.
authors.forename: Hyemyung
authors.initials: H
authors.lastname: Seo
authors.affiliation: Development and Differentiation Research Center, KRIBB, Yuseong-gu, Daejeon, 305-806, South Korea.|Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, South Korea.|Department of Functional Genomics, University of Science and Technology (UST), Yuseong-gu, Daejeon, 305-350, South Korea.
authors.forename: Yong-Kook
authors.initials: YK
authors.lastname: Kang
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D063146:Polycomb-Group Proteins / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D002843:Chromatin; D063146:Polycomb-Group Proteins
keywords: Huntingtin (HTT); Huntington’s disease; aging; chromatin accessibility; epigenetic; targeted NGS