Regulatory mechanisms of allelic exclusion by epigenetics and chromosome dynamics

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。

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.