Analysis of mechanism involved in the assembly balance between centromere chromatin and/or heterochromatin and in higher cellular regulation.

分析着丝粒染色质和/或异染色质之间的组装平衡以及高级细胞调节所涉及的机制。

• 批准号: 23247030
• 负责人: MASUMOTO Hiroshi
• 金额: $ 31.87万
• 依托单位: Kazusa DNA Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23247030/
• 关键词: 遺伝学; 染色体; ヘテロクロマチン; セントロメア; 人工染色体

We investigated mechanism involved in the chromatin assembly balance between centromere chromatin and/or heterochromatin at human centromeric repetitive alphoid DNA. We found that tethering of histone acetyltransferases (HATs) to alphoid DNA arrays broke a cell type-specific barrier (heterochromatin formation) for de novo stable CENP-A chromatin assembly and induced assembly of stable Human Artificial Chromosomes (HACs) with the input alphoid DNA. We, then, tethered a huge variety of tetR-fusion proteins to the tetO-alphoid HAC and screened many positive and negative regulators for the CENP-A chromatin assembly using KAZUSA full-length cDNA library. We also developed a system targeting the chromatin assembly balance at endogenous centromeres by fusing these regulators and CENP-B.

我们研究了人着丝粒重复α DNA中着丝粒染色质和/或异染色质组装平衡的机制。我们发现，组蛋白乙酰转移酶（HAT）的alphoid DNA阵列的拴系打破了从头稳定CENP-A染色质组装的细胞类型特异性障碍（异染色质形成），并诱导组装稳定的人类人工染色体（HAC）与输入alphoid DNA。然后，我们将大量tetR融合蛋白与tetO-α HAC连接，并使用KAZUSA全长cDNA文库筛选了许多CENP-A染色质组装的正调控因子和负调控因子。我们还通过融合这些调节因子和CENP-B开发了一个靶向内源性着丝粒的染色质组装平衡的系统。

项目成果

HP1γ links histone methylation marks to meiotic synapsis in mice

• DOI: 10.1242/dev.064444
• 发表时间: 2011-10-01
• 期刊: DEVELOPMENT
• 影响因子: 4.6
• 作者: Takada, Yuki;Naruse, Chie;Koseki, Haruhiko
• 通讯作者: Koseki, Haruhiko

セントロメア形成を決定するクロマチン集合バランス, 生体の科62(5)

决定着丝粒形成的染色质组装平衡，生物系 62(5)

• 发表时间: 2011
• 作者: Kageyama S;Omori H;Saitoh T;Sone T;Guan JL;Akira S;Imamoto F;Noda T;Yoshimori T;神川竜馬;舛本寛
• 通讯作者: 舛本寛

A method for CENP-A assembly

一种CENP-A组装方法

• 发表时间: 2012

The Analysis of regulation and maintenance mechanisms of centromere functional structure with chromatin-alterable human artificial chromosome system.

染色质可变的人类人工染色体系统对着丝粒功能结构的调控和维持机制分析。

• 发表时间: 2012
• 作者: Hirate;Y.;Nakano M.
• 通讯作者: Nakano M.

Protecting a transgene expression from the HAC-based vector by different chromatin insulators.

• DOI: 10.1007/s00018-013-1362-9
• 发表时间: 2013-10
• 期刊: CELLULAR AND MOLECULAR LIFE SCIENCES
• 影响因子: 8
• 作者: Lee, Nicholas Co;Kononenko, Artem V.;Lee, Hee-Sheung;Tolkunova, Elena N.;Liskovykh, Mikhail A.;Masumoto, Hiroshi;Earnshaw, William C.;Tomilin, Alexey N.;Larionov, Vladimir;Kouprina, Natalay
• 通讯作者: Kouprina, Natalay