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  1. C100 医学部/医学系研究科
  2. C100a 雑誌掲載論文
  3. 学術雑誌

Altered EZH2 splicing and expression is associated with impaired histone H3 lysine 27 tri-Methylation in myelodysplastic syndrome

http://hdl.handle.net/2237/00027924
http://hdl.handle.net/2237/00027924
3f3a5c6b-8e51-48c4-9f9e-9e9d638dd24c
名前 / ファイル ライセンス アクション
Shirahata_Adachi_Mizuho.pdf Shirahata_Adachi_Mizuho (5.7 MB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2018-04-19
タイトル
タイトル Altered EZH2 splicing and expression is associated with impaired histone H3 lysine 27 tri-Methylation in myelodysplastic syndrome
言語 en
著者 Shirahata-Adachi, Mizuho

× Shirahata-Adachi, Mizuho

WEKO 76206

en Shirahata-Adachi, Mizuho

Search repository
Iriyama, Chisako

× Iriyama, Chisako

WEKO 76207

en Iriyama, Chisako

Search repository
Tomita, Akihiro

× Tomita, Akihiro

WEKO 76208

en Tomita, Akihiro

Search repository
Suzuki, Yasuhiro

× Suzuki, Yasuhiro

WEKO 76209

en Suzuki, Yasuhiro

Search repository
Shimada, Kazuyuki

× Shimada, Kazuyuki

WEKO 76210

en Shimada, Kazuyuki

Search repository
Kiyoi, Hitoshi

× Kiyoi, Hitoshi

WEKO 76211

en Kiyoi, Hitoshi

Search repository
アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
権利
言語 en
権利情報 © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
キーワード
主題Scheme Other
主題 EZH2
キーワード
主題Scheme Other
主題 H3K27 methyltransferase
キーワード
主題Scheme Other
主題 Myelodysplastic syndromes
抄録
内容記述 Background: EZH2 (enhancer of zeste homolog 2) is a histone H3K27 methyltransferase involved in the pathogenesis of various hematological malignancies. In myelodysplastic syndromes (MDS), loss of function of EZH2 is known to contribute to pathogenesis, however the pattern of EZH2 mRNA and protein expression in MDS has not been extensively characterized. Material and methods: A total of 26 patients diagnosed with MDS were analyzed in this study. The relationship between EZH2 expression in patient bone marrow samples, evaluated by RT-PCR and immunoblotting, and patient characteristics were analyzed. The function of truncated EZH2 proteins was examined in vitro. Results: EZH2 expression levels and transcript sizes varied considerably between patients, but there was no relationship with the percentage blast component of patient samples. Cloning and sequencing of amplified RT-PCR fragments demonstrated that patients expressed multiple EZH2 transcripts containing insertions or deletions, with or without frameshift, mainly induced by altered splicing. All identified frameshift mutations were found to be 5′ to the functional SET domain, and resulted in truncated protein translation. Altered patterns of EZH2 expression was observed in patients with or without alterations in genes involved with RNA splicing, SRSF2, U2AF1 and SF3B1. Functional analysis in vitro revealed that C-terminally truncated EZH2, lacking the SET domain, may impair the methyltransferase function of wild-type EZH2 in a dominant negative fashion. Conclusion: Our findings suggest that the loss of function of EZH2 induced by aberrant splicing, and/or EZH2 mutations resulting in the production of C-terminally truncated proteins, may be involved in MDS pathogenesis.
言語 en
内容記述タイプ Abstract
内容記述
内容記述 ファイル公開日: 2018/12/01
言語 ja
内容記述タイプ Other
出版者
言語 en
出版者 Elsevier
言語
言語 eng
資源タイプ
資源タイプresource http://purl.org/coar/resource_type/c_6501
タイプ journal article
出版タイプ
出版タイプ AM
出版タイプResource http://purl.org/coar/version/c_ab4af688f83e57aa
DOI
関連タイプ isVersionOf
識別子タイプ DOI
関連識別子 https://doi.org/10.1016/j.leukres.2017.10.015
ISSN
収録物識別子タイプ PISSN
収録物識別子 01452126
書誌情報 en : Leukemia Research

巻 63, p. 90-97, 発行日 2017-12
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