A Study for Epigenetic Regulation to Maintain Cardiac Homeostasis

表观遗传调控维持心脏稳态的研究

• 批准号: 21689022
• 负责人: ASANO Yoshihiro
• 金额: $ 11.15万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (A)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21689022/
• 关键词: 分子心臓病態学; エピゲノム; ヘテロクロマチン; クロマチン免疫沈降法; 胎児性遺伝子; ヒストン修飾; ピストン修飾

Sustained gene activation, such as" cardiac fetal gene reactivation", has an important role in the mechanism underlying exacerbations of chronic heart failure. However, the maintenance mechanism of its expressional activation has not yet been fully elucidated. We first found evidence for heterochromatin disruption in the nucleus of failing cardiomyocytes and paradoxical depression of cis-acting transcription factors, despite elevated levels of target cardiac fetal genes, suggesting that epigenetic gene regulation might be involved in this phenomenon. In addition, we newly developed in vivo chromatin immunoprecipitation assay, which has hardly been applied in the field of cardiac tissue. The proven alteration in transcriptional sensitivity by epigenetic gene modification was found to play a significant role in the" nuclear memory" mediating heart failure, raising the hope for the novel pathological understanding for chronic diseases.

持续的基因激活，如“心脏胎儿基因再激活”，在慢性心力衰竭恶化的机制中起重要作用。然而，其表达激活的维持机制尚未完全阐明。我们首次发现，尽管靶心脏胎儿基因水平升高，但衰竭心肌细胞细胞核中的异染色质破坏和顺式作用转录因子的矛盾性抑制，表明表观遗传基因调控可能参与了这一现象。此外，我们还新开发了活体染色质免疫沉淀法，该方法在心脏组织领域的应用很少。经证实的表观遗传基因修饰导致的转录敏感性改变在“核记忆”介导心力衰竭中发挥了重要作用，这为对慢性疾病的新病理认识带来了希望。

项目成果

Development of anti-HB-EGF immunoliposomes for the treatment of breast cancer

• DOI: 10.1016/j.jconrel.2011.10.010
• 发表时间: 2012-06-10
• 期刊: JOURNAL OF CONTROLLED RELEASE
• 影响因子: 10.8
• 作者: Nishikawa, Kaoru;Asai, Tomohiro;Minamino, Tetsuo
• 通讯作者: Minamino, Tetsuo

Annual Review 2010 循環器

2010年度回顾心血管系统

• 发表时间: 2010
• 作者: Tasaki M;Ueda M;Ochiai S;Tanabe Y;Murata S;Su Y;Shinriki S;Jono H;Shono M;Obayashi K;Nakamura T;Yamada M;Ando Y.;泉家康宏
• 通讯作者: 泉家康宏

Ablation of C/EBP Homologous Protein Attenuates Endoplasmic Reticulum-Mediated Apoptosis and Cardiac Dysfunction Induced by Pressure Overload

• DOI: 10.1161/circulationaha.109.917914
• 发表时间: 2010-07-27
• 期刊: CIRCULATION
• 影响因子: 37.8
• 作者: Fu, Hai Ying;Okada, Ken-ichiro;Minamino, Tetsuo
• 通讯作者: Minamino, Tetsuo

AMPK controls the speed of microtubule polymerization and directional cell migration through CLIP-170 phosphorylation

• DOI: 10.1038/ncb2060
• 发表时间: 2010-06-01
• 期刊: NATURE CELL BIOLOGY
• 影响因子: 21.3
• 作者: Nakano, Atsushi;Kato, Hisakazu;Takashima, Seiji
• 通讯作者: Takashima, Seiji

X-box binding protein 1 regulates brain natriuretic peptide through a novel AP1/CRE-like element in cardiomyocyte

X-box结合蛋白1通过心肌细胞中的新型AP1/CRE样元件调节脑钠尿肽

• 发表时间: 2010
• 期刊: J Mol Cell Cardiol. (in press)
• 作者: Sawada T;et al.
• 通讯作者: et al.