Core promoter structure and genomic context reflect histone 3 lysine 9 acetylation patterns.
Core promoter structure and genomic context reflect histone 3 lysine 9 acetylation patterns.
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DOI：
10.1186/1471-2164-11-257
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发表时间：
2010-04-21
期刊：
影响因子：
4.4
通讯作者：
Daub CO
中科院分区：
文献类型：
--
作者：
Kratz A;Arner E;Saito R;Kubosaki A;Kawai J;Suzuki H;Carninci P;Arakawa T;Tomita M;Hayashizaki Y;Daub CO
组蛋白修饰在基因调控中发挥重要作用。组蛋白 3 赖氨酸 9 (H3K9ac) 的乙酰化通常与转录起始和展开染色质相关，从而对基因表达产生积极影响。使用 DeepCAGE 对基因转录本 5' 末端进行深度测序可提供有关基因启动子的结构和表达水平的详细信息。 H3K9ac ChIP 芯片和 DeepCAGE 在骨髓性白血病细胞系 (THP-1) 中的组合使我们能够使用一种新颖的聚类方法研究 H3K9ac 启动子周围的空间分布。分析启动子类别与相关基因组序列特征的关联。我们根据周围的 H3K9ac 信号对 4,481 个启动子进行了聚类，并分析了聚类的启动子与不同序列特征的关联。聚类揭示了启动子上游、中心和下游具有主要 H3K9ac 信号的三个组。窄单峰启动子往往在上游区域具有集中的 H3K9ac 活性，而宽启动子往往在中心和下游区域具有集中的 H3K9ac 和 RNA 聚合酶 II 结合活性。与具有低和中等基因表达水平的启动子子集相比，具有高基因表达水平的启动子子集仅在上游簇中表现出 H3K9ac 活性的显着增加；这可能表明中心和下游簇中的启动子主要在启动后步骤受到调节。此外，上游簇的 CpG 岛被耗尽，更有可能调节未注释的基因。根据核心启动子周围的乙酰化信号对其进行聚类是研究组蛋白修饰的一种有前途的方法。当检查根据周围 H3K9 乙酰化信号聚类的启动子时，我们发现 H3K9ac 的相对定位和强度非常具体，具体取决于启动子的特征序列特征。使用未分化（单核细胞）和分化（巨噬细胞）THP-1 细胞的 DeepCAGE 和 ChIP 芯片实验的实验数据使我们得出相同的结论。
Histone modifications play an important role in gene regulation. Acetylation of histone 3 lysine 9 (H3K9ac) is generally associated with transcription initiation and unfolded chromatin, thereby positively influencing gene expression. Deep sequencing of the 5' ends of gene transcripts using DeepCAGE delivers detailed information about the architecture and expression level of gene promoters. The combination of H3K9ac ChIP-chip and DeepCAGE in a myeloid leukemia cell line (THP-1) allowed us to study the spatial distribution of H3K9ac around promoters using a novel clustering approach. The promoter classes were analyzed for association with relevant genomic sequence features. We performed a clustering of 4,481 promoters according to their surrounding H3K9ac signal and analyzed the clustered promoters for association with different sequence features. The clustering revealed three groups with major H3K9ac signal upstream, centered and downstream of the promoter. Narrow single peak promoters tend to have a concentrated activity of H3K9ac in the upstream region, while broad promoters tend to have a concentrated activity of H3K9ac and RNA polymerase II binding in the centered and downstream regions. A subset of promoters with high gene expression level, compared to subsets with low and medium gene expression, shows dramatic increase in H3K9ac activity in the upstream cluster only; this may indicate that promoters in the centered and downstream clusters are predominantly regulated at post-initiation steps. Furthermore, the upstream cluster is depleted in CpG islands and more likely to regulate un-annotated genes. Clustering core promoters according to their surrounding acetylation signal is a promising approach for the study of histone modifications. When examining promoters clustered into groups according to their surrounding H3K9 acetylation signal, we find that the relative localization and intensity of H3K9ac is very specific depending on characteristic sequence features of the promoter. Experimental data from DeepCAGE and ChIP-chip experiments using undifferentiated (monocyte) and differentiated (macrophage) THP-1 cells leads us to the same conclusions.
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