Table_4_Genome-Wide Identification of Histone Modifications Involved in Placental Development in Pigs.XLS

Development of placental folds is a critical event affecting placental function in pigs because it can increase surface area for improvement in capillary density as gestation advances. However, the molecular mechanisms of the event are not well defined. Histone modifications have important roles in gene regulation. To investigate their effects on regulation of genes controlling porcine placental development, RNA-seq and ChIP-seq of porcine placental tissues from gestational days 50 (establishment stage of placental folds) and 95 (expanding stage of placental folds) were carried out in this study. The differentially expressed genes were identified and of which the down- and up-regulated genes are related to endoplasmic reticulum (ER) stress and angiogenesis, respectively. In addition, we mapped the genome-wide profiles of histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 acetylation (H3K27ac), which are associated with transcriptional activation. A number of differential modification regions between the 2 gestational stages were identified and majority of them are those with increased signals of H3K4me3 (14,576 out of 16,931). Furthermore, we observed that the increase of H3K4me3 is significantly correlated with the elevated expression levels of the neighboring genes, and notably, these genes were enriched in pathways related to blood vessel formation and microvascular permeability. Taken together, the findings suggest important roles of histone modifications on placental remolding in response to developmental changes.

胎盘褶皱发育是影响猪胎盘功能的关键事件——随着妊娠进程推进，该过程可通过增加表面积提升毛细血管密度。然而，这一过程的分子机制尚未得到明确阐释。组蛋白修饰在基因调控中发挥重要作用。为探究组蛋白修饰对调控猪胎盘发育相关基因的影响，本研究针对妊娠第50天（胎盘褶皱建立阶段）及第95天（胎盘褶皱扩张阶段）的猪胎盘组织，开展了RNA测序（RNA-seq）与染色质免疫共沉淀测序（ChIP-seq）实验。研究鉴定得到了差异表达基因，其中下调基因与内质网（ER）应激相关，而上调基因则与血管生成密切相关。此外，本研究绘制了与转录激活相关的两种组蛋白修饰——组蛋白H3赖氨酸4三甲基化（H3K4me3）与组蛋白H3赖氨酸27乙酰化（H3K27ac）的全基因组修饰图谱。研究共鉴定得到两个妊娠阶段间的大量差异修饰区域，其中绝大多数（16931个区域中的14576个）的H3K4me3信号显著上调。进一步分析发现，H3K4me3水平的上调与邻近基因的表达升高呈显著正相关；值得注意的是，这些邻近基因显著富集于血管生成及微血管通透性相关通路。综上，本研究结果表明，组蛋白修饰在响应发育变化的胎盘重塑过程中发挥了重要调控作用。