Pluripotency-related, Valproic Acid (VPA)-induced Genome-wide Histone H3 Lysine 9 (H3K9) Acetylation Patterns in Embryonic Stem Cells
Pluripotency-related, Valproic Acid (VPA)-induced Genome-wide Histone H3 Lysine 9 (H3K9) Acetylation Patterns in Embryonic Stem Cells
复制标题
DOI：
10.1074/jbc.m111.266254
复制
发表时间：
2011-10-14
影响因子：
4.8
通讯作者：
Meshorer, Eran
中科院分区：
文献类型：
--
作者：
Hezroni, Hadas;Sailaja, Badi Sri;Meshorer, Eran
背景：胚胎干细胞（ESC）染色质的特征在于一组独特的组蛋白修饰，包括富集H3 K9 ac。最近的研究表明，HDAC抑制剂（HDACi）促进多能性。使用H3 K9 ac ChIP-seq分析和用低水平HDACi丙戊酸（VPA）处理之前和之后E14小鼠ESC中的基因表达，我们表明H3 K9 ac在基因启动子处富集并且与基因表达和各种基因组特征高度相关，包括不同的活性组蛋白标记和多能性相关转录因子。结论：本研究提供了对ESCs对低水平HDACi的基因组应答的见解，这导致了多能性的增加。结果表明，染色质状态的温和（平均小于40%）但全局变化涉及多能性增加，并且特定机制选择性地在二价基因中操作以维持恒定的H3 K9 ac水平。我们的数据支持这一观点，即H3 K9 ac在ESC biology.Significance中具有重要作用：了解改善和支持ESC多能性的机制，例如使用HDAC抑制剂VPA，将促进ESC的智能操作并加快其在临床中的应用。
Background: Embryonic stem cell (ESC) chromatin is characterized by a unique set of histone modifications, including enrichment for H3K9ac. Recent studies suggest that HDAC inhibitors (HDACi) promote pluripotency.Results: Using H3K9ac ChIP-seq analyses and gene expression in E14 mouse ESCs before and after treatment with a low level of the HDACi valproic acid (VPA), we show that H3K9ac is enriched at gene promoters and is highly correlated with gene expression and with various genomic features, including different active histone marks and pluripotency-related transcription factors.Conclusion: This study provides insights into the genomic response of ESCs to low level HDACi, which leads to increased pluripotency. The results suggest that a mild (averaging less than 40%) but global change in the chromatin state is involved in increased pluripotency and that specific mechanisms operate selectively in bivalent genes to maintain constant H3K9ac levels. Our data support the notion that H3K9ac has an important role in ESC biology.Significance: Understanding the mechanisms that improve and support pluripotency of ESCs, such as the use of the HDAC inhibitor VPA, will promote intelligent manipulation of ESCs and expedite their use in the clinic.