Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra campus, Jerusalem, Israel.
Nucleus. 2011 Jul-Aug;2(4):300-9. doi: 10.4161/nucl.2.4.16767. Epub 2011 Jul 1.
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.
多能基因组的特征是独特的表观遗传特征和去凝聚的染色质构象。然而,表观遗传调控与多能性之间的关系并不完全清楚。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) 的重编程能力和组蛋白修饰,发现 E14 ESC 的能力显著降低,H3K9ac 水平显著降低。用组蛋白去乙酰化酶 (HDAC) 抑制剂 (HDACi) 处理 E14 ESC 可增加 H3K9ac 水平并恢复其重编程能力。微阵列和 H3K9ac ChIP-seq 分析表明,HDACi 处理后 E14 ESC 中细胞外基质 (ECM) 活性增加。这些数据表明,H3K9ac 可能预测多能性,并且通过 HDAC 抑制增加多能性可以通过 H3K9ac 增强涉及 ECM 产生的靶基因的活性,以支持多能性。