Division of Biological Sciences, 0377, Department of Molecular Biology, University of California, San Diego, La Jolla, CA, 92093, USA.
Princeton Center for Theoretical Science, Princeton University, Princeton, NJ, 08544, USA.
Nat Commun. 2019 Jun 24;10(1):2771. doi: 10.1038/s41467-019-10628-9.
Diverse antibody repertoires are generated through remote genomic interactions involving immunoglobulin variable (V), diversity (D) and joining (J) gene segments. How such interactions are orchestrated remains unknown. Here we develop a strategy to track V-DJ motion in B-lymphocytes. We find that V and DJ segments are trapped in configurations that allow only local motion, such that spatially proximal segments remain in proximity, while spatially remote segments remain remote. Within a subset of cells, however, abrupt changes in V-DJ motion are observed, plausibly caused by temporal alterations in chromatin configurations. Comparison of experimental and simulated data suggests that constrained motion is imposed by a network of cross-linked chromatin chains characteristic of a gel phase, yet poised near the sol phase, a solution of independent chromatin chains. These results suggest that chromosome organization near the sol-gel phase transition dictates the timing of genomic interactions to orchestrate gene expression and somatic recombination.
多样化的抗体库是通过涉及免疫球蛋白可变 (V)、多样性 (D) 和连接 (J) 基因片段的远程基因组相互作用产生的。这些相互作用是如何协调的仍然未知。在这里，我们开发了一种跟踪 B 淋巴细胞中 V-DJ 运动的策略。我们发现 V 和 DJ 片段被捕获在仅允许局部运动的构象中，使得空间上邻近的片段保持接近，而空间上远程的片段保持远程。然而，在一小部分细胞中，观察到 V-DJ 运动的突然变化，可能是由染色质构象的时间变化引起的。实验数据和模拟数据的比较表明，受约束的运动是由交联染色质链网络施加的，这些链网络的特征是凝胶相，但接近于溶胶相，即独立染色质链的溶液。这些结果表明，溶胶-凝胶相变附近的染色体组织决定了基因组相互作用的时间，以协调基因表达和体细胞重组。
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