文章摘要
丁 蓉,胡毓华,何思思,陆 超.转录因子THAP1在人肺泡Ⅱ型上皮细胞中结合靶基因的谱系分析[J].南京医科大学学报,2015,(9):1200~1204
转录因子THAP1在人肺泡Ⅱ型上皮细胞中结合靶基因的谱系分析
Profiling analysis of target genes binded by transcription factor THAP1 in human alveolar type Ⅱ epithelial cells
投稿时间:2015-04-17  
DOI:10.7655/NYDXBNS20150903
中文关键词: 高通量测序  A549 细胞  THAP1  染色质免疫共沉淀实验
英文关键词: high-throughput sequencing  A549 cells  THAP1  ChIP
基金项目:国家自然科学基金(81170487);江苏省妇幼系统重点学科项目(FXK 201212)
作者单位
丁 蓉 南京医科大学第一附属医院儿科,江苏 南京 210036 
胡毓华 南京医科大学第一附属医院儿科,江苏 南京 210036 
何思思 南京医科大学第一附属医院儿科,江苏 南京 210036 
陆 超 南京医科大学第一附属医院儿科,江苏 南京 210036 
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中文摘要:
      目的:确定转录因子THAP1的靶基因,为新生儿肺损伤的治疗寻找新策略。方法:利用THAP1抗体进行染色质免疫共沉淀实验(chromatin immuno-precipitation,ChIP),将富集到肺泡Ⅱ型上皮细胞来源的肺腺癌细胞A549上的DNA样品进行高通量测序,对得到的核苷酸序列进行生物信息学分析。结果:共得到20 417个THAP1结合位点的核苷酸序列片段,对应9 688个结合的靶基因,THAP1结合的主要区域分布在基因间区?内含子区和启动子区。其中包含1 051个基因的启动子区。将THAP1结合于启动子区的基因进行基因功能(gene ontology,GO)注释,表明THAP1参与包括蛋白质二聚化?同源蛋白质结合?蛋白质磷酸化调节?类固醇激素受体的激活等多种细胞生物学过程。THAP1结合的基因主要涉及9个代谢路径,以胞吞作用?多糖降解?硫酸软骨素或硫酸皮肤素的生物合成等路径为主。结论:初步确定了转录因子THAP1在肺泡Ⅱ型上皮细胞中的靶基因结合序列,提示THAP1广泛参与了多种生物学过程,为研究THAP1的功能及作用机制研究提供了线索,从而为新生儿肺损伤的治疗奠定了基础。
英文摘要:
      Objective:To determine target genes of transcription factors THAP1 for a new therapeutic strategy of neonatal lung injury. Methods:Chromatin DNA in alveolar type Ⅱ epithelial cells was immunoprecipitated with THAP1 antibody. The obtained DNA samples were then subjected to high-throughput sequencing and bioinformatic analysis. Results:A total 20 417 enrichment peaks corresponding 9 688 genes was found. The mapping of the peaks revealed that the targeted nucleotide sequences located mainly within intergenic regions,intron regions and promoter regions,which contained 1 051 gene promoter regions. Gene Ontology(GO)analysis suggested that THAP1 regulated a set of genes,which were involved in various biological processes including protein dimerization activity,identical protein binding,protein phosphatase regulator activity,steroid hormone receptor activity. Signal pathway analysis showed that these genes were associated with endocytosis,glycan degradation,and biosynthesis-chondroitin sulfate/dermatan sulfate. Conclusion:The targeted genes of the transcription factor THAP1 in the alveolar type Ⅱ epithelial cells were determined. These results show that THAP1 is widely involved in various biological processes,which might provide a useful insight to reveal the function and mechanism of THAP1 gene on neonatal lung injury.
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