Deacetylation of Histone H4 Accompanying Cardiomyogenesis is Weakened in HDAC1-Depleted ES Cells.
Deacetylation of Histone H4 Accompanying Cardiomyogenesis is Weakened in HDAC1-Depleted ES Cells.
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DOI：
10.3390/ijms19082425
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发表时间：
2018-08-16
影响因子：
5.6
通讯作者：
Bártová E
中科院分区：
文献类型：
--
作者：
Arcidiacono OA;Krejčí J;Suchánková J;Bártová E
细胞分化为心肌细胞需要激活分化特异性基因和表观遗传因子，这些基因和表观遗传因子有助于这些生理过程。本研究旨在体外诱导小鼠胚胎干细胞向心肌细胞分化。还分析了临床上有前途的组蛋白脱乙酰酶（HDACi）抑制剂对mESC心肌发生和对移植的胚胎心脏的影响。HDAC1耗竭引起心肌细胞的早期跳动相比，野生型（野生型）对应。此外，HDAC1双敲除（dn）的胚胎干细胞（EB）的粘附减少。最重要的发现是在wt mESCs的心肌细胞分化期间观察到的分化特异性H4脱乙酰化，而在诱导至心脏途径的HDAC1耗尽的细胞中H4脱乙酰化减弱。HDACi作用的分析显示曲古抑菌素A（TSA）是一种强的超乙酰化剂，尤其是在wt mESC中，但只有SAHA减小了源自HDAC1和mESC的EB中的搏动区域的大小。此外，胚胎心脏（e15）对HDACi治疗有反应：所有测试的HDACi（TSA、SAHA、VPA）增加胚胎心脏中H3K9ac、H4ac、H4K20ac和全乙酰化赖氨酸的水平。这一观察结果表明，切除的组织在切除后几小时可以保持在超乙酰化状态，这从移植策略和通过乙酰化维持用于移植的组织中的基因上调的观点来看似乎是有用的信息。
Cell differentiation into cardiomyocytes requires activation of differentiation-specific genes and epigenetic factors that contribute to these physiological processes. This study is focused on the in vitro differentiation of mouse embryonic stem cells (mESCs) induced into cardiomyocytes. The effects of clinically promising inhibitors of histone deacetylases (HDACi) on mESC cardiomyogenesis and on explanted embryonic hearts were also analyzed. HDAC1 depletion caused early beating of cardiomyocytes compared with those of the wild-type (wt) counterpart. Moreover, the adherence of embryonic bodies (EBs) was reduced in HDAC1 double knockout (dn) mESCs. The most important finding was differentiation-specific H4 deacetylation observed during cardiomyocyte differentiation of wt mESCs, while H4 deacetylation was weakened in HDAC1-depleted cells induced to the cardiac pathway. Analysis of the effect of HDACi showed that Trichostatin A (TSA) is a strong hyperacetylating agent, especially in wt mESCs, but only SAHA reduced the size of the beating areas in EBs that originated from HDAC1 dn mESCs. Additionally, explanted embryonic hearts (e15) responded to treatment with HDACi: all of the tested HDACi (TSA, SAHA, VPA) increased the levels of H3K9ac, H4ac, H4K20ac, and pan-acetylated lysines in embryonic hearts. This observation shows that explanted tissue can be maintained in a hyperacetylation state several hours after excision, which appears to be useful information from the view of transplantation strategy and the maintenance of gene upregulation via acetylation in tissue intended for transplantation.
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影响因子：
49.6
作者：
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通讯作者：
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