Regulation of T cell development mediated by BAF complex and Runx3

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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.