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A role for Gcn5 in cardiomyocyte differentiation of rat mesenchymal stem cells
Li, Li3; Zhu, Jing1; Tian, Jie2; Liu, Xiaoyan2; Feng, Chuan2
关键词Mesenchymal stem cells Differentiation Cardiomyocyte Gcn5 Histone acetylation HAT activity
刊名MOLECULAR AND CELLULAR BIOCHEMISTRY
2010-12-01
DOI10.1007/s11010-010-0586-3
345期:1-2页:309-316
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell Biology
资助者National Natural Science Foundation of China ; National Natural Science Foundation of China
研究领域[WOS]Cell Biology
关键词[WOS]HISTONE ACETYLTRANSFERASE ; IN-VIVO ; GENE ACTIVATION ; YEAST ; CHROMATIN ; COACTIVATORS ; ACETYLATION ; PROMOTER ; TRANSCRIPTION ; RECRUITMENT
英文摘要

MSCs possess the capacity of self-renewal and potential of differentiation into various kinds of specialized tissue cells including myocardiocytes. From self-renewing to oriented differentiation, chromatin is remodeled into heritable states that allow activation or maintain the repression of regulatory genes, which means specific genes in self-renewing switched off and specific genes in oriented differentiation activated (Bernstein et al. Cell 125:315-326, 2006). These epigenetic states are established and controlled largely by specific patterns of histone posttranslational modifications, in particular, histone acetylation (Li Nat Rev Genet 3:662-673, 2002). In cardiomyocyte differentiation of rat MSCs, we focused on Gcn5, which linked a known transcriptional coactivator with catalytic histone acetyltransferase activity (Brownell et al. Cell 84:843-851, 1996). To clarify participatory in vivo role of Gcn5, using an RNA interference (RNAi) strategy employing shRNA to specifically knockdown Gcn5 expression in MSCs, we found that HAT activity altered dynamically depended on the inhibition of Gcn5 during MSCs differentiation. Chromatin immunoprecipitation (ChIP) assay showed the increased binding of acetyl histone H3 to the early cardiomyocyte-specific genes GATA4 and NKx2.5 promoters in cardiomyocyte differentiation of MSCs by 5-azacytidine inducing, whereas the decreased binding with lower Gcn5 expression. Cell ultrastructure analysis revealed that MSCs induced by 5-azacytidine possess morphological characteristics of cardiomyocyte cells. The shape of MSCs transfected by Gcn5 RNAi was similar to normal MSCs, but the chromatin showed heavy electron-density and a hard-packed structure. This intermediate state of chromatin may be an inactive part of MSCs differentiation. These results demonstrate that Gcn5, possessing acetyltransferase activity, is involved in regulating chromatin configuration around GATA4 and NKx2.5 in cardiomyocyte differentiation of rat MSCs by changing the level of histone acetylation. HAT activity depending on Gcn5 is important in differentiation of MSCs into cardiomyocytes as a consequence of the remodeling of the chromatin configuration caused by modification of histone H3.

语种英语
所属项目编号30670871 ; 30901621
资助者National Natural Science Foundation of China ; National Natural Science Foundation of China
WOS记录号WOS:000284907100032
引用统计
被引频次:12[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61031
专题北京大学第一临床医学院_儿科
作者单位1.Chongqing Med Univ, Dept Sci Res, Childrens Hosp, Chongqing 400014, Peoples R China
2.Chongqing Med Univ, Dept Cardiol, Childrens Hosp, Chongqing 400014, Peoples R China
3.Peking Univ, Dept Pediat, Hosp 1, Beijing 100034, Peoples R China
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GB/T 7714
Li, Li,Zhu, Jing,Tian, Jie,et al. A role for Gcn5 in cardiomyocyte differentiation of rat mesenchymal stem cells[J]. MOLECULAR AND CELLULAR BIOCHEMISTRY,2010,345(1-2):309-316.
APA Li, Li,Zhu, Jing,Tian, Jie,Liu, Xiaoyan,&Feng, Chuan.(2010).A role for Gcn5 in cardiomyocyte differentiation of rat mesenchymal stem cells.MOLECULAR AND CELLULAR BIOCHEMISTRY,345(1-2),309-316.
MLA Li, Li,et al."A role for Gcn5 in cardiomyocyte differentiation of rat mesenchymal stem cells".MOLECULAR AND CELLULAR BIOCHEMISTRY 345.1-2(2010):309-316.
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