Genome-Wide Identification of Histone Modifications Involved in Placental Development in Pigs

Genome-Wide Identification of Histone Modifications Involved in Placental Development in Pigs
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猪胎盘发育中涉及的组蛋白修饰的全基因组鉴定

DOI:
10.3389/fgene.2019.00277
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发表时间:
2019-03-29
影响因子:
3.7
通讯作者:
Yu, Mei
Yu, Mei
中科院分区:
生物学3区
文献类型:
--
作者:
Han, Kun;Ren, Ruimin;Yu, Mei

文献摘要

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胎盘皱襞的发育是影响猪胎盘功能的关键事件,因为随着妊娠的进展,胎盘皱襞可以增加表面积以改善毛细血管密度。然而,该事件的分子机制尚不清楚。组蛋白修饰在基因调控中具有重要作用。为了研究它们对控制猪胎盘发育的基因调控的影响,本研究对妊娠第 50 天(胎盘皱襞形成阶段)和 95 天(胎盘皱襞展开阶段)的猪胎盘组织进行了 RNA-seq 和 ChIP-seq。鉴定了差异表达的基因,其中下调和上调的基因分别与内质网(ER)应激和血管生成相关。此外,我们还绘制了组蛋白 H3 赖氨酸 4 三甲基化 (H3K4me3) 和组蛋白 H3 赖氨酸 27 乙酰化 (H3K27ac) 的全基因组图谱,这些图谱与转录激活相关。确定了两个妊娠阶段之间的许多差异修饰区域,其中大多数是 H3K4me3 信号增加的区域(16,931 个中的 14,576 个)。此外,我们观察到H3K4me3的增加与邻近基因表达水平的升高显着相关,值得注意的是,这些基因在与血管形成和微血管通透性相关的通路中富集。总而言之,这些发现表明组蛋白修饰在响应发育变化的胎盘重塑中发挥重要作用。
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.