CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China.
Genomics Proteomics Bioinformatics. 2012 Apr;10(2):82-93. doi: 10.1016/j.gpb.2012.05.007. Epub 2012 Jun 9.
The global features of H3K4 and H3K27 trimethylations (H3K4me3 and H3K27me3) have been well studied in recent years, but most of these studies were performed in mammalian cell lines. In this work, we generated the genome-wide maps of H3K4me3 and H3K27me3 of mouse cerebrum and testis using ChIP-seq and their high-coverage transcriptomes using ribominus RNA-seq with SOLiD technology. We examined the global patterns of H3K4me3 and H3K27me3 in both tissues and found that modifications are closely-associated with tissue-specific expression, function and development. Moreover, we revealed that H3K4me3 and H3K27me3 rarely occur in silent genes, which contradicts the findings in previous studies. Finally, we observed that bivalent domains, with both H3K4me3 and H3K27me3, existed ubiquitously in both tissues and demonstrated an invariable preference for the regulation of developmentally-related genes. However, the bivalent domains tend towards a "winner-takes-all" approach to regulate the expression of associated genes. We also verified the above results in mouse ES cells. As expected, the results in ES cells are consistent with those in cerebrum and testis. In conclusion, we present two very important findings. One is that H3K4me3 and H3K27me3 rarely occur in silent genes. The other is that bivalent domains may adopt a "winner-takes-all" principle to regulate gene expression.
近年来,H3K4 和 H3K27 三甲基化(H3K4me3 和 H3K27me3)的全球特征已得到深入研究,但这些研究大多是在哺乳动物细胞系中进行的。在这项工作中,我们使用 ChIP-seq 生成了小鼠大脑和睾丸的 H3K4me3 和 H3K27me3 的全基因组图谱,并使用 SOLiD 技术的 ribominus RNA-seq 生成了其高覆盖率转录组。我们检查了这两种组织中 H3K4me3 和 H3K27me3 的全局模式,发现修饰与组织特异性表达、功能和发育密切相关。此外,我们揭示了 H3K4me3 和 H3K27me3 很少发生在沉默基因中,这与以前的研究结果相矛盾。最后,我们观察到,具有 H3K4me3 和 H3K27me3 的双价结构域在两种组织中普遍存在,并表现出对发育相关基因调控的不变偏好。然而,双价结构域倾向于采用“胜者通吃”的方式来调控相关基因的表达。我们还在小鼠 ES 细胞中验证了上述结果。不出所料,ES 细胞中的结果与大脑和睾丸中的结果一致。总之,我们提出了两个非常重要的发现。一是 H3K4me3 和 H3K27me3 很少发生在沉默基因中。另一个是双价结构域可能采用“胜者通吃”的原则来调控基因表达。