Study about Tubulin protein's novel function in interphase nuclei and regulation by polycomb proteins.

微管蛋白在间期核中的新功能及多梳蛋白的调控研究。

• 批准号: 21657046
• 负责人: FUJIMURA Yu-ichi
• 金额: $ 2.18万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 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-21657046/
• 关键词: 核ラミナ; クロマチン; チュブリン; ヒストンアセチル化; HDAC; 核内分子局在; nuclear lamina; HDACs; 核内微小構造

In metazoan, the inner surface of nuclear envelope is lined by nuclear lamina(NL), primarily consist of Lamins. Physical interaction of NL and intranuclear molecules engages in regulation of chromosome statement and of transcriptional activity. Large extent of the genes associating to NL is transcriptionally repressed. NL also associates to variety of chromatin modifying factors including HDACs. Given that histone acetylation at nuclear periphery in low level and is close involved in transcriptional activity of genes interacting to NL, these molecular associations make proximal space of NL a microdomain which promotes deacetylation of histone, and thereby transcriptional repression.However, machineries which link NL and its binding factors in living cells are yet poorly understood. Here we show Tubulin proteins persistently associate to NL, and are indispensable for association of NL-chromatin, and of NL-HDACs. Loss of Tubulin from NL results in the disengagement of chromatin and HDACs from NL, and upregulation of histone acetylation at nuclear periphery. Moreover, we found association of Tubulin and chromatin requires polycomb group(PcG) protein Ring1b, therefore Ring1b mediates binding of chromatin and NL. Our data show novel function of Tubulin proteins and PcGs for the molecular assembly determinative for chromosome statement at nuclear periphery.

在后生动物中，核膜内表面衬有核纤层（NL），主要由核纤层组成。NL和核内分子的物理相互作用参与染色体陈述和转录活性的调节。与NL相关的大部分基因都受到转录抑制。NL还与包括HDAC在内的多种染色质修饰因子相关。由于组蛋白乙酰化水平较低，且与NL相互作用基因的转录活性密切相关，这些分子缔合使NL近端空间成为促进组蛋白去乙酰化的微区，从而抑制转录。在这里，我们表明微管蛋白蛋白持续与NL相关，并且对于NL-染色质和NL-HDAC的缔合是必不可少的。微管蛋白从NL的丢失导致染色质和HDAC从NL脱离，以及核周边组蛋白乙酰化的上调。此外，我们发现微管蛋白和染色质的结合需要多梳组（PcG）蛋白Ring 1b，因此Ring 1b介导染色质和NL的结合。我们的数据显示了微管蛋白和PcGs在分子组装中的新功能，该分子组装决定了核周边染色体的状态。

项目成果

Sall4 Is Essential for Stabilization, But Not for Pluripotency, of Embryonic Stem Cells by Repressing Aberrant Trophectoderm Gene Expression

• DOI: 10.1002/stem.14
• 发表时间: 2009-01-01
• 期刊: STEM CELLS
• 影响因子: 5.2
• 作者: Yuri, Shunsuke;Fujimura, Sayoko;Nishinakamura, Ryuichi
• 通讯作者: Nishinakamura, Ryuichi

Bmil is a MYCN target gene that regulates tumorigenesis through repression of KIF1Bbeta and TSLC1 in neuroblastoma.

Bmil 是 MYCN 靶基因，通过抑制神经母细胞瘤中的 KIF1Bbeta 和 TSLC1 来调节肿瘤发生。

• 发表时间: 2010
• 期刊: Oncogene 29
• 作者: Ochiai H;Takenobu H;Nakagawa A;Yamaguchi Y;Kimura M;Ohira M;Okimoto Y;Fujimura Y;Koseki H;Kohno Y;Nakagawara A;Kamijo T.
• 通讯作者: Kamijo T.