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徐薇, 庄志雄, 杨建平等. 细胞复制衰老过程中IGF2R基因表达及H3组蛋白修饰的变化[J]. koko体育app 学报（医学版）, 2014, 45(1): 6-9.
引用本文: 徐薇, 庄志雄, 杨建尊重. 体细胞重命名萎缩工作中IGF2R基因组理解及H3组蛋清装饰的变动[J]. 安徽高中学报（中医药学版）, 2014, 45(1): 6-9.
XU Wei, ZHUANG Zhi-xiong, YANG Jian-ping. et al. The Profile of IGF2RGene Expression and H3 Histone Modifications in Replicative Cell Senescence[J]. Journal of Sichuan University (Medical Sciences), 2014, 45(1): 6-9.
Citation: XU Wei, ZHUANG Zhi-xiong, YANG Jian-ping. et al. The Profile of IGF2RGene Expression and H3 Histone Modifications in Replicative Cell Senescence[J]. Journal of Sichuan University (Medical Sciences), 2014, 45(1): 6-9.

细胞复制衰老过程中IGF2R基因表达及H3组蛋白修饰的变化

The Profile of IGF2RGene Expression and H3 Histone Modifications in Replicative Cell Senescence

  • 摘要: 目的 研究细胞复制性衰老过程中胰岛素样生长因子2受体基因（IGF2R）的表达与H3组蛋白修饰谱的变化。 方法 培养人胚肺成纤维细胞（HPF），以细胞群倍增数(PDL)为23(PDL23)为年轻组细胞，PDL=50(PDL50)为复制衰老细胞，观察细胞复制衰老过程中生物学性状改变；采用实时定量PCR法观察细胞PDL30、PDL40、PDL50 IGF2R基因的表达, 并采用染色质免疫共沉淀-实时定量PCR法（chromatinimmunoprecipitation-real time quantitative PCR methods,CHIP-PCR）检测IGF2R基因转录起始区组蛋白修饰(H3-Ac、H3K9-tri-Me、H3K9-Ac和H3K4-tri-Me) 的状况。 结果 与年轻细胞相比，衰老细胞体积变大，增殖能力减弱，细胞周期停滞，衰老特异性β-半乳糖苷酶着色阳性，IGF2R mRNA表达增加（PIGF2R mRNA表达与细胞PDL呈正相关(r=0.871)。相对年轻细胞而言，老年细胞的IGF2R基因在转录起始点上游0.6 kb处和转录起始点下游1.2 kb处以H3-Ac、H3K9-Ac和H3K4-tri-Me组蛋白修饰为主，而在转录起始点下游1.6~4.0 kb处H3K9-Ac修饰降低，H3K9-tri-Me组蛋白修饰升高，但H3K4-tri-Me组蛋白修饰占主要地位。 结论 IGF2R与细胞衰老程度相关，其基因表达受H3组蛋白修饰调控，表观遗传学参与细胞衰老进程。  
    Abstract: Objective?To study the profile of IGF2R expression and histone modifications in replicative cell senescence. Methods?The changes of biological characteristics of young human pulmonary fibroblast (HPF) cells 〔at population doubling level (PDL) 23〕 and aging HPF cells (at PDL50) were observed and real-time quantitative PCR was utilized to investigate human IGF2R gene expressions profile during the process of cellular aging (at different PDL). Then chromatinimmunoprecipitation-real time quantitative PCR (CHIP-QPCR) methods were conducted to analyze histone modifications of the regions around the transcriptional start site of IGF2R (H3-Ac, H3K9-tri-Me, H3K9-Ac and H3K4-tri-Me). Results?In contrast to young cells, the aging cells were bigger and less proliferative, their cell cycles arrest, and aging specific β-galactosidase staining was positive. IGF2R gene expression was in positive correlation with PDL. H3-Ac, H3K9-Ac and H3K4-tri-Me were dominant in the upstream region (-0.6 kb) to the downstream region (+1.2 kb) of transcriptional start site (TSS). While in the downstream of TSS from +1.6 kb to +4.0 kb, H3K9-Ac was declined and H3K9-tri-Me was elevated in turn, but H3K4-tri-Me still prevailed in these areas. Conclusion?IGF2R is related to cell replicative senescence and its gene expression is regulated by histone modification of H3. Therefore, epigenetics may play a role in cell senescence.  
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