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细胞沿着多条途径分化,伴随着组蛋白乙酰化状态的变化。

Cell differentiation along multiple pathways accompanied by changes in histone acetylation status.

机构信息

a Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Královopolská 135, 612 65 Brno, Czech Republic.

出版信息

Biochem Cell Biol. 2014 Apr;92(2):85-93. doi: 10.1139/bcb-2013-0082. Epub 2014 Jan 17.

DOI:10.1139/bcb-2013-0082
PMID:24697692
Abstract

Post-translational modification of histones is fundamental to the regulation of basic nuclear processes and subsequent cellular events, including differentiation. In this study, we analyzed acetylated forms of histones H2A, H2B, and H4 during induced differentiation in mouse (mESCs) and human (hESCs) embryonic stem cells and during induced enterocytic differentiation of colon cancer cells in vitro. Endoderm-like differentiation of mESCs induced by retinoic acid and enterocytic differentiation induced by histone deacetylase inhibitor sodium butyrate were accompanied by increased mono-, di-, and tri-acetylation of histone H2B and a pronounced increase in di- and tri-acetylation of histone H4. In enterocytes, mono-acetylation of histone H2A also increased and tetra-acetylation of histone H4 appeared only after induction of this differentiation pathway. During differentiation of hESCs, we observed increased mono-acetylation and decreased tri-acetylation of H2B. Mono-, di-, and tri-acetylation of H4 were reduced, manifested by a significant increase in nonacetylated H4 histones. Levels of acetylated histones increased during induced differentiation in mESCs and during histone deacetylase (HDAC) inhibitor-induced enterocytic differentiation, whereas differentiation of human ESCs was associated with reduced acetylation of histones H2B and H4.

摘要

组蛋白的翻译后修饰对于基本核过程和随后的细胞事件(包括分化)的调节至关重要。在这项研究中,我们分析了在体外诱导的小鼠(mESCs)和人类(hESCs)胚胎干细胞分化以及结肠癌细胞诱导的肠细胞分化过程中组蛋白 H2A、H2B 和 H4 的乙酰化形式。维甲酸诱导的 mESC 内胚层样分化和组蛋白去乙酰化酶抑制剂丁酸钠诱导的肠细胞分化伴随着组蛋白 H2B 的单、二和三乙酰化增加,以及组蛋白 H4 的二乙酰化和三乙酰化明显增加。在肠细胞中,组蛋白 H2A 的单乙酰化也增加,并且只有在诱导这种分化途径后才出现组蛋白 H4 的四乙酰化。在 hESC 分化过程中,我们观察到 H2B 的单乙酰化增加和三乙酰化减少。H4 的单、二和三乙酰化减少,表现为非乙酰化 H4 组蛋白的显著增加。在 mESCs 诱导分化过程中和组蛋白去乙酰化酶(HDAC)抑制剂诱导的肠细胞分化过程中,乙酰化组蛋白的水平增加,而 hESC 的分化与组蛋白 H2B 和 H4 的乙酰化减少有关。

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