表观调控因子CFP1 在T 细胞分化发育中的机制研究

Cfp1是一个关键的表观遗传调控分子，可以分别通过与DNMT1和Setd1结合参与DNA甲基化以及组蛋白H3K4me3修饰的调控。我们非常感兴趣其在T淋巴细胞的分化发育中的作用。由于全基因组敲除Cfp1会导致胚胎致死，因此我们构建了Cfp1条件性敲除小鼠。与hCD2cre，Lckcre ，CD4cre等T细胞特异性转基因小鼠进行杂交，以达到在T细胞发育不同时期敲除Cfp1基因的目的。敲除Cfp1导致严重的胸腺内T细胞发育受阻，主要表现在CD4+ CD8+双阳性细胞，CD4+单阳性细胞以及CD8+单阳性细胞数目与比例明显下降。为了阐明其中的机制，我们计划利用CHIP-seq（染色质免疫沉淀）与MeDIP-seq（甲基化的DNA免疫沉淀）等方法确定Cfp1调控的靶基因以及其调控方式,从而为T淋巴细胞表观调控研究带来新的思路。

Cfp1 is key regulator of both cytosine methylation and H3-Lys4 tri-methylation (H3K4me3) by associated with Dnmt1, and the set1 complex respectively. We are interested in its function in T cell development , Since Cfp1 genomic knockout mice is embryonic lethal, We generated Cfp1 conditional knockout mice and found that loss the Cfp1 in developing T cell using hCD2cre or Lckcre transgene mice led to severe developmental block, evident by a drastic reduction of CD4+CD8+ double positive (DP), CD4+SP and CD8+SP cell number. To elucidate the underlying mechanism, We plan to use CHIP-seq (chromatin immunoprecipitation) and MeDIP-seq (methylated DNA immunoprecipitation) technology to definite the targets and the mechanism of Cfp1.