Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution.
Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution.
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DOI：
10.1371/journal.pone.0012339
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发表时间：
2010-08-23
期刊：
影响因子：
3.7
通讯作者：
Vetrie D
中科院分区：
文献类型：
--
作者：
Dhami P;Saffrey P;Bruce AW;Dillon SC;Chiang K;Bonhoure N;Koch CM;Bye J;James K;Foad NS;Ellis P;Watkins NA;Ouwehand WH;Langford C;Andrews RM;Dunham I;Vetrie D
最近已经表明，核小体分布、组蛋白修饰和RNA聚合酶II（Pol II）占据显示与外显子的优先关联（“外显子-内含子标记”），将染色质结构和功能与多种真核生物中的共转录剪接联系起来。以前的ChIP测序研究表明，这些标记模式反映了核小体景观。通过分析三种细胞类型中人类基因组的ChIP芯片数据集，我们发现这种标记系统比以前观察到的要复杂得多。我们在这里表明，一系列的组蛋白修饰和Pol II优先与外显子。然而，在组蛋白修饰的外显子标记程度中存在明显的细胞类型特异性，并且令人惊讶的是，这也反映在一些组蛋白修饰模式中，其显示出对内含子的偏好。外显子-内含子标记是在沉默基因没有转录的情况下进行的，对于不同水平表达的基因，一些标记偏好会发生变化或逆转。此外，这种标记系统与剪接的关系并不简单，只有一些组蛋白修饰反映了外显子的使用/包含，而另一些则反映了外显子排除的模式。通过检查核小体分布在所有三种细胞类型，我们表明，这些组蛋白修饰模式不能单独占外显子和内含子之间的核小体水平的差异。此外，由于ChIP芯片阵列和ChIP测序方法之间的固有差异，这些平台报告了人类基因组中不同的核小体分布模式。我们的研究结果混淆了现有的观点，并指出积极的细胞机制，动态调节组蛋白修饰水平和占外显子-内含子标记。我们相信这些组蛋白修饰模式提供了染色质可及性、Pol II运动和共转录剪接之间的联系。
It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons (“exon-intron marking”), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing.
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