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H3K9 histone acetylation predicts pluripotency and reprogramming capacity of ES cells

机译：H3K9组蛋白乙酰化预测ES细胞的多能性和重编程能力

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摘要

The pluripotent genome is characterized by unique epigenetic features and a decondensed chromatin conformation. However, the relationship between epigenetic regulation and pluripotency is not altogether clear. Here, using an enhanced MEF/ESC fusion protocol, we compared the reprogramming potency and histone modifications of different embryonic stem cell (ESC) lines (R1, J1, E14, C57BL/6) and found that E14 ESCs are significantly less potent, with significantly reduced H3K9ac levels. Treatment of E14 ESCs with histone deacetylase (HDAC) inhibitors (HDACi) increased H3K9ac levels and restored their reprogramming capacity. Microarray and H3K9ac ChIP-seq analyses, suggested increased extracellular matrix (ECM) activity following HDACi treatment in E14 ESCs. These data suggest that H3K9ac may predict pluripotency and that increasing pluripotency by HDAC inhibition acts through H3K9ac to enhance the activity of target genes involved in ECM production to support pluripotency.
机译：多能基因组的特征是独特的表观遗传学特征和不浓缩的染色质构象。然而，表观遗传调控与多能性之间的关系尚不清楚。在这里，我们使用增强的MEF / ESC融合方案，比较了不同胚胎干细胞（ESC）系（R1，J1，E14，C57BL / 6）的重编程效能和组蛋白修饰，发现E14 ESC的效能明显较低，大大降低了H3K9ac水平。用组蛋白脱乙酰基酶（HDAC）抑制剂（HDACi）处理E14 ESC可提高H3K9ac水平并恢复其重编程能力。芯片和H3K9ac ChIP-seq分析表明，在E14 ESC中进行HDACi处理后，细胞外基质（ECM）活性增加。这些数据表明，H3K9ac可以预测多能性，并且通过HDAC抑制而增加的多能性可通过H3K9ac发挥作用，从而增强参与ECM生产的靶基因的活性以支持多能性。

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