Regulatory mechanisms of allelic exclusion by epigenetics and chromosome dynamics

表观遗传学和染色体动力学等位基因排除的调控机制

• 批准号: 20590298
• 负责人: AGATA Yasutoshi
• 金额: $ 3万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590298/
• 关键词: エピジェネティクス; クロマチン; 対立遺伝子排除; 転写因子; 遺伝子発現; エピジェネテクス; 染色体ダイナミクス; 遺伝子再構成

The E2A transcription factor binds directly to genetic regions in the TCRβ locus and induces rearrangement by increasing histone acetylation. We analyzed the contraction and decontraction status of the TCRβ locus by 3D-FISH and found that V and DJ regions come into the close proximity during the stage in which rearrangement normally occurs, but become separated away from each other during the stage in which further rearrangement is inhibited. We also found that E2A overexpression induces localization of the V and DJ regions into the close proximity even in the stage in which further rearrangement is inhibited, and finally induces the rearrangement. These results suggest that E2A has the ability of inducing rearrangement not only by epigenetic changes but also by chromosome dynamics including locus contraction.

E2 A转录因子直接与TCRβ基因座中的遗传区域结合，并通过增加组蛋白乙酰化诱导重排。我们通过3D-FISH分析了TCRβ基因座的收缩和去收缩状态，发现在正常重排发生的阶段，V和DJ区域非常接近，但在进一步重排被抑制的阶段，V和DJ区域彼此分离。我们还发现，E2 A过表达诱导的V和DJ区域的本地化到接近，即使在进一步的重排被抑制的阶段，并最终诱导重排。这些结果表明，E2 A具有诱导重排的能力，不仅通过表观遗传变化，但也通过染色体动力学，包括位点收缩。

项目成果

Regulation of TCR Vγ2 gene rearrangement by the helix-loop-helix protein, E2A.

螺旋-环-螺旋蛋白 E2A 对 TCR Vγ2 基因重排的调节。

• DOI: 10.1093/intimm/dxr005
• 发表时间: 2011
• 期刊: I lit Immunol.
• 作者: Nozaki M;Wakae K;Tamaki N;Sakamoto S;Ohnishi K;Uejima T;Minato N;Yanagihara I;Agata Y
• 通讯作者: Agata Y

Regulation of Vγ2 gene rearrangement by the helix-loop-helix protein, E2A.

螺旋-环-螺旋蛋白 E2A 对 Vγ2 基因重排的调节。

• 发表时间: 2010
• 作者: Sumida H;Noguchi K;Kihara Y;Abe M;Yanagida K;Hamano F;Sato S;Tamaki K;Morishita Y;Kano MR.;Iwata C;Miyazono K;Sakimura K;Shimizu T;Ishii S;橋本あり;野崎昌俊
• 通讯作者: 野崎昌俊

Claudin-4 induction by E-protein activity in later stages of CD4/8 double-positive thymocytes to increase positive selection efficiency

• DOI: 10.1073/pnas.1014178108
• 发表时间: 2011-03-08
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Kawai, Yohei;Hamazaki, Yoko;Minato, Nagahiro
• 通讯作者: Minato, Nagahiro

The NF90-NF45 Complex Functions as a Negative Regulator in the MicroRNA Processing Pathway

• DOI: 10.1128/mcb.01836-08
• 发表时间: 2009-07-01
• 期刊: MOLECULAR AND CELLULAR BIOLOGY
• 影响因子: 5.3
• 作者: Sakamoto, Shuji;Aoki, Kazuma;Agata, Yasutoshi
• 通讯作者: Agata, Yasutoshi

E2A and CBP/p300 act in synergy to promote chromatin accessibility of the immunoglobulin κlocus in nonlymphoid cells.

E2A 和 CBP/p300 协同作用，促进非淋巴细胞中免疫球蛋白 κ 位点染色质的可及性。

• 发表时间: 2010
• 作者: Ouchida R.;Yamasaki S.;Hikida M.;Masuda K.;Kawamura K.;Wada A.;Mochizuki S.;Tagawa M.;Sakamoto A.;Hatano M.;Tokuhisa T.;Koseki H.;Saito T.;Kurosaki T.;Wang Ji-Y.;松井雪子,喜多紗斗美,伊豫田拓也,桂木猛,小室一成,岩本隆宏,大慈弥裕之;縣保年
• 通讯作者: 縣保年