衰老细胞染色质开放变化的初步分析

Chromatin Accessibility Dynamics in Replicative Senescence

为研究复制性衰老中表观遗传学的变化,以年轻代龄(PD26)和年老代龄(PD55)的人胚肺二倍体成纤维细胞(2BS)为材料,进行ATAC-seq测序,并使用Bowtie2、FastQC、MACS、deepTools、phastCons、R语言、HOMER以及基因本体论(Gene Ontology,GO)对测序结果进行深入分析和挖掘。结果显示,2BS细胞染色质开放区域的保守性较强,其主要集中于启动子(promoter)区至转录起始位点(transcription start site,TSS),且年轻细胞与年老细胞的启动子区至转录起始位点的开放程度不同,细胞随着衰老在启动子区至转录起始位点的开放程度逐渐下降。进一步对年轻和年老细胞之间存在显著差异的靶基因进行GO分析发现,这些差异基因主要与细胞进程、代谢、生物性调节、结合功能、催化功能相关。本次研究发现衰老过程中染色质开放区减少、转录调控水平下降,提示复制性衰老与转录调控关系密切。

To study the epigenetic changes in replicative senescence,the ATAC-seq was performed in young(PD26)and senescent(PD55)2BS cells.After sequencing,the results were analyzed by Bowtie2,FastQC,MACS,deepTools,phastCons,R language,HOMER and Gene Ontology(GO).The enrichment sites of open chromatin regions were highly conserved.Although the open regions were mainly enriched between the promoter and transcription start site(TSS),the enrichments in the young and the old are not the same,varying with aging of 2BS cells.Furthermore,GO analysis was performed to analyze the differentially expressed genes in different ages of 2BS cells.The genes were mainly clustered in cellular process,metabolic process,biological regulation,binding and so on.These results showed that the aging process was accompanied by declined degree of chromatin openness and decreased level of transcriptional regulation,which revealed the close relationship between the replicative senescence and transcriptional regulation.