编码和调节DNA元素采用的3D轨迹:基因组相互作用的第一通道时间
Joseph S Lucas1, Yaojun Zhang2, Olga K Dudko2
1Division of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA.
Cell
|July 8, 2014
概括
由于细胞的内部环境,B细胞受体的基因段随机移动. 空间限制显著影响了这些DNA元素在适当的基因组装中相互找到的速度.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- B淋巴细胞的发育需要免疫球蛋白重链变量 (VH),多样性 (DH) 和连接 (JH) 基因段的组合,以创建多样化的抗原受体谱.
- 了解核内的这些基因组元素的三维 (3D) 组织和动态对于破译V(D) J重组的机制至关重要.
研究的目的:
- 在B淋巴细胞发育过程中调查VH和DH-JH-Emicro区域的3D轨迹和动态.
- 模拟这些基因组元素的运动,并确定影响它们相互作用的因素.
主要方法:
- 标记远端VH和DH-JH-Emicro区域与亲B细胞中的Tet-运营商结合点.
- 使用活细胞成像在表达Tet-repressor-EGFP的细胞中追踪这些标记区域的3D轨迹.
- 应用分数朗格温动力学 (fLm) 建模来分析观察到的运动和相互作用.
主要成果:
- VH和DH-JH-Emicro元素呈现分数朗格温运动,表明核环境的粘弹性障碍.
- 分数朗格温动力学建模预测了DHJH元素在几分钟内遇到VH元素的高概率.
- 空间限制被确定为控制这些关键基因组接触的频率的主要因素.
结论:
- 核的粘弹性特性会影响免疫球蛋白基因段在发育过程中的动态行为.
- 拓领域的空间限制在调节V(D) J重组的基本基因组相互作用时间方面发挥着重要作用.
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