Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 민선준 | - |
dc.date.accessioned | 2018-07-18T02:05:18Z | - |
dc.date.available | 2018-07-18T02:05:18Z | - |
dc.date.issued | 2017-11 | - |
dc.identifier.citation | ACTA NEUROPATHOLOGICA, v. 134, No. 5, Page. 729-748 | en_US |
dc.identifier.issn | 1432-0533 | - |
dc.identifier.issn | 0001-6322 | - |
dc.identifier.uri | https://link.springer.com/article/10.1007%2Fs00401-017-1732-8 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/72653 | - |
dc.description.abstract | Huntington's disease (HD) is an autosomal-dominant inherited neurological disorder caused by expanded CAG repeats in exon 1 of the Huntingtin (HTT) gene. Altered histone modifications and epigenetic mechanisms are closely associated with HD suggesting that transcriptional repression may play a pathogenic role. Epigenetic compounds have significant therapeutic effects in cellular and animal models of HD, but they have not been successful in clinical trials. Herein, we report that dSETDB1/ESET, a histone methyltransferase (HMT), is a mediator of mutant HTT-induced degeneration in a fly HD model. We found that nogalamycin, an anthracycline antibiotic and a chromatin remodeling drug, reduces trimethylated histone H3K9 (H3K9me3) levels and pericentromeric heterochromatin condensation by reducing the expression of Setdb1/Eset. H3K9me3-specific ChIP-on-ChIP analysis identified that the H3K9me3-enriched epigenome signatures of multiple neuronal pathways including Egr1, Fos, Ezh1, and Arc are deregulated in HD transgenic (R6/2) mice. Nogalamycin modulated the expression of the H3K9me3-landscaped epigenome in medium spiny neurons and reduced mutant HTT nuclear inclusion formation. Moreover, nogalamycin slowed neuropathological progression, preserved motor function, and extended the life span of R6/2 mice. Together, our results indicate that modulation of SETDB1/ESET and H3K9me3-dependent heterochromatin plasticity is responsible for the neuroprotective effects of nogalamycin in HD and that small compounds targeting dysfunctional histone modification and epigenetic modification by SETDB1/ESET may be a rational therapeutic strategy in HD. | en_US |
dc.description.sponsorship | This study was supported by NIH Grant (R01 NS067283 and R01AG054156) (H.R.). This study was also supported by the National Research Foundation of Korea Grant (NRF-2015M3A9A8030034 and NRF-2016M3C7A1904233) from the Ministry of Science, ICT and Future Planning, the National Research Council of Science and Technology (NST) Grant (No. CRC-15-04-KIST) from the Korea government (MSIP), and Grants from Korea Institute of Science and Technology (2E26200 and 2E26663). | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | SPRINGER | en_US |
dc.subject | Huntington's disease | en_US |
dc.subject | Heterochromatin | en_US |
dc.subject | Histone methyltransferase | en_US |
dc.subject | H3K9me3 | en_US |
dc.subject | Epigenome | en_US |
dc.subject | HISTONE DEACETYLASE INHIBITORS | en_US |
dc.subject | H3 LYSINE-9 METHYLATION | en_US |
dc.subject | TRANSGENIC MOUSE MODEL | en_US |
dc.subject | CREB-BINDING PROTEIN | en_US |
dc.subject | POLYGLUTAMINE TOXICITY | en_US |
dc.subject | MAMMALIAN CHROMATIN | en_US |
dc.subject | GENE-EXPRESSION | en_US |
dc.subject | NERVOUS-SYSTEM | en_US |
dc.subject | DNA-BINDING | en_US |
dc.subject | TRANSCRIPTION | en_US |
dc.title | Remodeling of heterochromatin structure slows neuropathological progression and prolongs survival in an animal model of Huntington's disease | en_US |
dc.type | Article | en_US |
dc.relation.no | 5 | - |
dc.relation.volume | 134 | - |
dc.identifier.doi | 10.1007/s00401-017-1732-8 | - |
dc.relation.page | 729-748 | - |
dc.relation.journal | ACTA NEUROPATHOLOGICA | - |
dc.contributor.googleauthor | Lee, Junghee | - |
dc.contributor.googleauthor | Hwang, Yu Jin | - |
dc.contributor.googleauthor | Kim, Yunha | - |
dc.contributor.googleauthor | Lee, Min Young | - |
dc.contributor.googleauthor | Hyeon, Seung Jae | - |
dc.contributor.googleauthor | Lee, Soojin | - |
dc.contributor.googleauthor | Kim, Dong Hyun | - |
dc.contributor.googleauthor | Jang, Sung Jae | - |
dc.contributor.googleauthor | Im, Hyoenjoo | - |
dc.contributor.googleauthor | Min, Sun-Joon | - |
dc.contributor.googleauthor | Choo, Hyunah | - |
dc.contributor.googleauthor | Pae, Ae Nim | - |
dc.contributor.googleauthor | Kim, Dong Jin | - |
dc.contributor.googleauthor | Cho, Kyung Sang | - |
dc.contributor.googleauthor | Kowall, Neil W. | - |
dc.contributor.googleauthor | Ryu, Hoon | - |
dc.relation.code | 2017002967 | - |
dc.sector.campus | E | - |
dc.sector.daehak | COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E] | - |
dc.sector.department | DEPARTMENT OF CHEMICAL AND MOLECULAR ENGINEERING | - |
dc.identifier.pid | sjmin | - |
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