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学科主题: 临床医学
题名:
A role for Gcn5 in cardiomyocyte differentiation of rat mesenchymal stem cells
作者: 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
发表日期: 2010-12-01
DOI: 10.1007/s11010-010-0586-3
卷: 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
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
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000284907100032
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61031
Appears in Collections:北京大学第一临床医学院_儿科_期刊论文

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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

Recommended Citation:
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.
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