Regulatory mechanisms of allelic exclusion by epigenetics and chromosome dynamics

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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.