Islet-1 synergizes with Gcn5 to promote MSC differentiation into cardiomyocytes
Islet-1 synergizes with Gcn5 to promote MSC differentiation into cardiomyocytes
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Islet-1与Gcn5协同促进MSC分化为心肌细胞
DOI：
10.1038/s41598-020-58387-8
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发表时间：
2020-02
期刊：
影响因子：
--
通讯作者：
Jing Zhu
中科院分区：
文献类型：
--
作者：
Hao Xu;Qin Zhou;Qin Yi;Bin Tan;Jie Tian;Xueni Chen;Yue Wang;Xia Yu;Jing Zhu
间充质干细胞(MSCs)可以特异性地分化为心肌细胞，作为逆转心肌损伤疾病的潜在途径，揭示这种分化机制是非常重要的。我们先前已经证明，组蛋白乙酰化/甲基化和DNA甲基化参与了胰岛-1诱导的MSC向心肌细胞的分化。这些修饰通过在心脏特异基因的启动子区域相互作用来调节这些基因，但这些相互作用的分子机制尚不清楚。在本研究中，我们发现调控GATA4/NKX2.5表达的关键酶是Gcn5/HDAC1、G9a和DNMT-1。当用α-亚甲基-γ-丁内酯3(MB-3)抑制GCN5的表达时，我们观察到GATA4/NKX2.5启动子中这些关键酶之间的相互作用被阻断，MSCs不能被诱导为心肌细胞。结果表明，胰岛-1可以诱导Gcn5与GATA4/NKX2.5启动子区域结合，并诱导Gcn5、HDAC1、G9a和DNMT-1之间的相互作用，上调GATA4/NKX2.5的表达，促进MSC向心肌细胞分化。
Mesenchymal stem cells (MSCs) specifically differentiate into cardiomyocytes as a potential way to reverse myocardial injury diseases, and uncovering this differentiation mechanism is immensely important. We have previously shown that histone acetylation/methylation and DNA methylation are involved in MSC differentiation into cardiomyocytes induced by islet-1. These modifications regulate cardiac-specific genes by interacting with each other in the promoter regions of these genes, but the molecular mechanism of these interactions remains unknown. In this study, we found that the key enzymes that regulate GATA4/Nkx2.5 expression are Gcn5/HDAC1, G9A, and DNMT-1. When α-methylene-γ-butyrolactone 3 (MB-3) was used to inhibit Gcn5 expression, we observed that the interactions among these key enzymes in the GATA4/Nkx2.5 promoters were blocked, and MSCs could not be induced into cardiomyocytes. Our results indicated that islet-1 could induce Gcn5 binding to GATA4/Nkx2.5 promoter regions and induce the interactions among Gcn5, HDAC1, G9A and DNMT-1, which upregulated GATA4/Nkx2.5 expression and promoted MSC differentiation into cardiomyocytes.
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影响因子：
9.2
作者：
Lehnertz, B;Ueda, Y;Peters, AHFM
通讯作者：
Peters, AHFM
影响因子：
3.7
作者：
Khajeniazi, Safoura;Solati, Mahin;Kianmehr, Anvarsadat
通讯作者：
Kianmehr, Anvarsadat
DOI：
10.1016/j.bbagrm.2008.07.009
发表时间：
2009-01
影响因子：
4.7
作者：
Marmorstein, Ronen;Trievel, Raymond C.
通讯作者：
Trievel, Raymond C.
间充质干细胞分化为心肌细胞样细胞期间，组蛋白修饰与 GATA4 启动子处的 DNA 甲基化相互作用
影响因子：
8.5
作者：
Xu, Hao;Yi, Qin;Zhu, Jing
通讯作者：
Zhu, Jing
DOI：
10.1152/ajpcell.00359.2012
发表时间：
2013-06
期刊：
American journal of physiology. Cell physiology
影响因子：
--
作者：
Meijing Wang;Qing Yu;Lina Wang;Hongmei Gu
通讯作者：
Meijing Wang;Qing Yu;Lina Wang;Hongmei Gu