Gene regulation shapes the evolution of phenotypic diversity. We investigated the evolution of liver promoters and enhancers in six primate species using ChIP-seq (H3K27ac and H3K4me1) to profile cis-regulatory elements (CREs) and using RNA-seq to characterize gene expression in the same individuals. To quantify regulatory divergence, we compared CRE activity across species by testing differential ChIP-seq read depths directly measured for orthologous sequences. We show that the primate regulatory landscape is largely conserved across the lineage, with 63% of the tested human liver CREs showing similar activity across species. Conserved CRE function is associated with sequence conservation, proximity to coding genes, cell-type specificity, and transcription factor binding. Newly evolved CREs are enriched in immune response and neurodevelopmental functions. We further demonstrate that conserved CREs bind master regulators, suggesting that while CREs contribute to species adaptation to the environment, core functions remain intact. Newly evolved CREs are enriched in young transposable elements (TEs), including Long-Terminal-Repeats (LTRs) and SINE-VNTR-Alus (SVAs), that significantly affect gene expression. Conversely, only 16% of conserved CREs overlap TEs. We tested the cis-regulatory activity of 69 TE subfamilies by luciferase reporter assays, spanning all major TE classes, and showed that 95.6% of tested TEs can function as either transcriptional activators or repressors. In conclusion, we demonstrated the critical role of TEs in primate gene regulation and illustrated potential mechanisms underlying evolutionary divergence among the primate species through the noncoding genome.

基因调控决定了表型多样性的演变。我们使用芯片起（H3K27ac和H3K4me1），以轮廓调查肝脏启动子和增强的演变六个灵长类物种顺-调节元件（CRE），并使用RNA-seq表征同一个体中的基因表达。为了量化监管差异，我们通过测试直接为直系同源序列测量的差异ChIP-seq读取深度，比较了物种间的CRE活性。我们表明，在整个血统中，灵长类动物的监管格局在很大程度上是保守的，其中63％的人类肝脏CRE在物种间表现出相似的活性。保守的CRE功能与序列保守，与编码基因的接近程度，细胞类型特异性和转录因子结合有关。新近发展的CRE丰富了免疫反应和神经发育功能。我们进一步证明了保守的CRE与主调节剂结合，这表明尽管CRE有助于物种对环境的适应，但核心功能仍保持不变。Alu s（SVA），显着影响基因表达。相反，只有16％的保守CRE与TE重叠。我们通过萤光素酶报告基因检测法测试了69个TE亚家族的顺式调节活性，这些测定法涵盖了所有主要的TE类，并显示95.6％的受测TE可以充当转录激活因子或阻遏物。总之，我们证明了TEs在灵长类动物基因调控中的关键作用，并阐明了通过非编码基因组在灵长类动物之间进化差异背后的潜在机制。