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胚胎发生过程中,增强子染色质特征的动态变化标志着从多能性到细胞特化的转变。

Dynamics of enhancer chromatin signatures mark the transition from pluripotency to cell specification during embryogenesis.

机构信息

Centro Andaluz de Biología del Desarrollo, CSIC-UPO-JA, 41013 Sevilla, Spain.

出版信息

Genome Res. 2012 Oct;22(10):2043-53. doi: 10.1101/gr.134833.111. Epub 2012 May 16.

Abstract

The generation of distinctive cell types that form different tissues and organs requires precise, temporal and spatial control of gene expression. This depends on specific cis-regulatory elements distributed in the noncoding DNA surrounding their target genes. Studies performed on mammalian embryonic stem cells and Drosophila embryos suggest that active enhancers form part of a defined chromatin landscape marked by histone H3 lysine 4 mono-methylation (H3K4me1) and histone H3 lysine 27 acetylation (H3K27ac). Nevertheless, little is known about the dynamics and the potential roles of these marks during vertebrate embryogenesis. Here, we provide genomic maps of H3K4me1/me3 and H3K27ac at four developmental time-points of zebrafish embryogenesis and analyze embryonic enhancer activity. We find that (1) changes in H3K27ac enrichment at enhancers accompany the shift from pluripotency to tissue-specific gene expression, (2) in early embryos, the peaks of H3K27ac enrichment are bound by pluripotent factors such as Nanog, and (3) the degree of evolutionary conservation is higher for enhancers that become marked by H3K27ac at the end of gastrulation, suggesting their implication in the establishment of the most conserved (phylotypic) transcriptome that is known to occur later at the pharyngula stage.

摘要

不同组织和器官的特有细胞类型的产生需要对基因表达进行精确、时间和空间上的控制。这取决于其靶基因周围非编码 DNA 中分布的特定顺式调控元件。在哺乳动物胚胎干细胞和果蝇胚胎中的研究表明,活性增强子形成了由组蛋白 H3 赖氨酸 4 单甲基化(H3K4me1)和组蛋白 H3 赖氨酸 27 乙酰化(H3K27ac)标记的特定染色质景观的一部分。然而,人们对这些标记在脊椎动物胚胎发生过程中的动态及其潜在作用知之甚少。在这里,我们提供了斑马鱼胚胎发生四个发育时间点的 H3K4me1/me3 和 H3K27ac 的基因组图谱,并分析了胚胎增强子活性。我们发现:(1)增强子中 H3K27ac 富集的变化伴随着从多能性到组织特异性基因表达的转变;(2)在早期胚胎中,H3K27ac 富集的峰被多能因子如 Nanog 结合;(3)在原肠胚晚期被 H3K27ac 标记的增强子的进化保守程度更高,这表明它们在建立已知在咽囊阶段后期发生的最保守(典型)转录组中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ee4/3460198/652ebe254362/2043fig1.jpg

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