Epigenetic modifications are associated with inter-species gene expression variation in primates

Changes in gene regulation level have long been thought to play an important role in evolution and speciation, especially in primates. Over the past decade, comparative genomic studies have revealed extensive inter-species differences in gene expression levels yet we know much less about the extent to which regulatory mechanisms differ between species. To begin addressing this gap, we performed a comparative epigenetic study in primate lymphoblastoid cell lines (LCLs), to query the contribution of RNA polymerase II (Pol II) and four histone modifications (H3K4me1, H3K4me3, H3K27ac, and H3K27me3) to inter-species variation in gene expression levels. We found that inter-species differences in mark enrichment near transcription start sites are significantly more often associated with inter-species differences in the corresponding gene expression level than expected by chance alone. Interestingly, we also found that first-order interactions among the histone marks and Pol II do not markedly contribute to the degree of association between the marks and inter-species variation in gene expression levels, suggesting that the marginal effects of the five marks dominate this contribution. Overall design: ChIP-seq of RNA polymerase II and 4 histone modifications (H3K4me1, H3K4me3, H3K27ac, H3K27me3), and RNA-seq, in 8 chimpanzee and 8 rhesus macaque lymphoblastoid cell lines

长期以来，基因调控水平的变化被学界认为在演化与物种形成过程中发挥关键作用，这一点在灵长类动物中尤为突出。近十年来，比较基因组学研究已揭示出物种间基因表达水平存在广泛差异，但我们对不同物种间调控机制的差异程度却了解极为有限。为填补这一研究空白，我们针对灵长类淋巴母细胞系（lymphoblastoid cell lines, LCLs）开展了比较表观遗传学研究，以探究RNA聚合酶II（RNA polymerase II, Pol II）与四种组蛋白修饰（H3K4me1、H3K4me3、H3K27ac及H3K27me3）对物种间基因表达水平差异的贡献程度。我们发现，转录起始位点附近的修饰富集程度所存在的物种间差异，与对应基因表达水平的物种间差异的关联程度，显著高于随机概率下的预期水平。有趣的是，我们还发现，组蛋白修饰与Pol II之间的一级相互作用，并未显著影响修饰与基因表达水平物种间差异之间的关联程度，这表明五种修饰的边际效应主导了这一贡献过程。实验整体设计：对8株黑猩猩与8株恒河猴的淋巴母细胞系开展RNA聚合酶II及4种组蛋白修饰（H3K4me1、H3K4me3、H3K27ac、H3K27me3）的染色质免疫沉淀测序（ChIP-seq），以及转录组测序（RNA-seq）。