Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Cell Rep. 2012 Jul 26;2(1):62-8. doi: 10.1016/j.celrep.2012.05.019. Epub 2012 Jul 20.
Here, we explore the role of splicing in transcription, employing both genome-wide analysis of human ChIP-seq data and experimental manipulation of exon-intron organization in transgenic cell lines. We show that the activating histone modifications H3K4me3 and H3K9ac map specifically to first exon-intron boundaries. This is surprising, because these marks help recruit general transcription factors (GTFs) to promoters. In genes with long first exons, promoter-proximal levels of H3K4me3 and H3K9ac are greatly reduced; consequently, GTFs and RNA polymerase II are low at transcription start sites (TSSs) and exhibit a second, promoter-distal peak from which transcription also initiates. In contrast, short first exons lead to increased H3K4me3 and H3K9ac at promoters, higher expression levels, accuracy in TSS usage, and a lower frequency of antisense transcription. Therefore, first exon length is predictive for gene activity. Finally, splicing inhibition and intron deletion reduce H3K4me3 levels and transcriptional output. Thus, gene architecture and splicing determines transcription quantity and quality as well as chromatin signatures.
在这里，我们探讨了剪接在转录中的作用，采用了人类 ChIP-seq 数据的全基因组分析和转基因细胞系中外显子-内含子组织的实验操作。我们表明，激活组蛋白修饰 H3K4me3 和 H3K9ac 特异性地映射到第一外显子-内含子边界。这令人惊讶，因为这些标记有助于招募一般转录因子（GTFs）到启动子。在具有长第一外显子的基因中，H3K4me3 和 H3K9ac 的启动子近端水平大大降低；因此，GTFs 和 RNA 聚合酶 II 在转录起始位点（TSS）处含量较低，并表现出第二个启动子远端峰，转录也从该峰起始。相比之下，短的第一外显子导致启动子处的 H3K4me3 和 H3K9ac 增加、表达水平更高、TSS 使用的准确性更高以及反义转录的频率更低。因此，第一外显子的长度可预测基因的活性。最后，剪接抑制和内含子缺失降低了 H3K4me3 水平和转录输出。因此，基因结构和剪接决定了转录的数量和质量以及染色质特征。
