Regulation of T cell development mediated by BAF complex and Runx3

发育中的胸腺细胞为研究胸腺分化过程中染色质结构的变化提供了有用的工具。根据先前的结果，Runx3在CD8胸腺细胞的发育中起着关键作用(Sato T.，et.艾尔。这项研究旨在阐明通过Runx3的功能对CD8胸腺细胞进行谱系选择的分子基础。研究表明，染色质重构分子BAF复合体控制CD4和8的表达非常类似于Runx3。这增加了Runx3与BAF复合体结合并协调调节CD4和8表达的可能性。在研究中，我发现DNA复制的控制在谱系确定过程中起着一些重要的作用。阻断DNA复制可抑制CD8胸腺细胞的分化，而DNA复制增强可抑制CD8胸腺细胞的分化。由于DNA复制伴随着染色质结构的动态变化，DNA复制控制对谱系确定过程的影响在不久的将来还有待阐明。

Developing thymocytes provide a useful tool to investigate the changes of the chromatin structure in the differentiation process. Based on the previous result that Runx3 plays pivotal roles in the development of CD8 thymocytes (Sato T., et. Al. Immunity 2005), this study has been designed to clarify the molecular basis for the lineage choice to CD8 thymocytes through the function of Runx3.This study revealed that chromatin re-modeler BAF complex controls CD4 and 8 expression quite similarly to Runx3. This raised the possibility that Runx3 binds to BAF complex and coordinately regulate CD4 and 8 expressions. In the study, I found that the control of DNA replication play some important roles in the lineage determination process. Blockade of DNA replication inhibited CD8 thymocytes differentiation, whereas augmentation of DNA replication inhibited CD4 thymocytes differentiation. Since DNA replication is accompanied with dynamic change of chromatin structure, it is to be clarified how DNA replication control affect on the lineage determination process in near future.