【作者】 于磊；

【导师】 张阳德；

【作者基本信息】 中南大学 ， 生物医学工程， 2013， 博士

【摘要】 本研究旨在探索转录因子CEBPB (CCAAT enhancer-binding protein β, CCAAT增强结合蛋白β)在全反式维甲酸(ATRA, All-trans retinoic acid)诱导急性早幼粒细胞白血病(APL, acute promyelocytic leukemia)细胞分化的调控机制。应用染色质免疫沉淀技术(ChIP)和体外筛选相结合的方法进行高通量分析(high throughput assay),确定CEBPB的下游靶基因。一百零六个CEBPB的结合片段从ATRA诱导NB4细胞的基因组(genome)中选出。其中,82个片段在已知或先前预测的基因中找到；其中,随机取出7片段用ChIP-PCR方法进一步确认,最后,确认3个基因(GALM, ITPR2和ORM2)在ARTA诱导NB4细胞中高表达(up-regulated),这表明它们可能是转录因子CEBPB的下游靶基因。该实验结果对揭示ATRA诱导粒细胞分化的机制提供了新的启发。图25幅,表2个,参考文献164篇更多还原

【Abstract】 This study is to explore the mechanism of transcription factor CEBPB (CCAAT enhancer-binding protein β) in regulation of the acute promyelocytic leukemia (APL) cell differentiation induced by All-trans retinoic acid (ATRA). The method of combining chromatin immunoprecipitation (ChIP) with in vitro selection was applied for high-throughput identification of the CEBPB downstream direct target genes. One Hundred and six CEBPB binding fragments from the genome of the ATRA-treated NB4cells were selected after ChIP. Among them,82were mapped in proximity to the known or previously predicted genes; meanwhile,7were randomly picked up for further confirmation by ChIP-PCR and finally3genes (GALM, ITPR2and ORM2) were found to be specifically up-regulated in ATRA-treated NB4cells, indicating that they might be the down-stream target genes of transcription factor CEBPB. The results provide a new insight into the mechanisms of ATRA-induced granulocytic differentiation.更多还原