Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Michigan Medicine, Ann Arbor, MI, USA.
Department of Surgery, Michigan Medicine, Ann Arbor, MI, USA.
FEBS J. 2019 Jan;286(1):82-109. doi: 10.1111/febs.14728. Epub 2018 Dec 22.
Chorioamnionitis is an intrauterine infection involving inflammation of the chorion, amnion, and placenta. It leads to a fetal systemic inflammatory response that can alter the transcription of neonatal immune genes. We have previously shown that neonatal monocytes gain the activating histone tail modification H3K4me3 at promoter sites of immunologically important genes as development progresses from preterm neonate to adult. In this study, we applied ChIP-seq and RNA-seq to evaluate the impact of chorioamnionitis on the neonatal monocyte H3K4me3 histone modification landscape over the course of fetal and neonatal immune system development. Chorioamnionitis exposure in neonatal monocytes resulted in a net increase in total monocyte H3K4me3, primarily in introns and intergenic regions. Immune gene expression was decreased in chorioamnionitis-exposed monocytes, with the majority of enriched transcripts falling into pathways that are not linked to the immune system. Over half of all neonatal monocyte H3K4me3 peaks, independent of their location, were associated with active gene transcription. Overall, chorioamnionitis exposure resulted in the global remodeling of the neonatal monocyte H3K4me3 landscape and changes in the expression of known immune genes. These changes resulted in a less robust inflammatory response upon exposure to a secondary challenge, which may explain why chorioamnionitis-exposed neonates have an increased risk of sepsis. DATABASE: ChIP-seq data for U30/O30/Term: GEO GSE81957 ChIP-seq data for U30C/O30C/TermC: GEO GSE111873 RNA-seq data for U/L/CU/CL: GEO GSE111927.
绒毛膜羊膜炎是一种宫内感染，涉及绒毛膜、羊膜和胎盘的炎症。它导致胎儿全身炎症反应，从而改变新生儿免疫基因的转录。我们之前已经表明，随着从早产儿到成人的发育过程，新生儿单核细胞在免疫重要基因的启动子位点获得激活组蛋白尾部修饰 H3K4me3。在这项研究中，我们应用 ChIP-seq 和 RNA-seq 来评估绒毛膜羊膜炎对胎儿和新生儿免疫系统发育过程中新生儿单核细胞 H3K4me3 组蛋白修饰图谱的影响。在新生儿单核细胞中暴露于绒毛膜羊膜炎会导致单核细胞总 H3K4me3 的净增加，主要是在内含子和基因间区域。在暴露于绒毛膜羊膜炎的单核细胞中，免疫基因表达减少，大多数富集的转录本落入与免疫系统无关的途径中。超过一半的新生儿单核细胞 H3K4me3 峰，无论其位置如何，都与活跃的基因转录有关。总的来说，绒毛膜羊膜炎暴露导致新生儿单核细胞 H3K4me3 图谱的全局重塑，以及已知免疫基因表达的变化。这些变化导致在暴露于二次挑战时炎症反应减弱，这可能解释为什么暴露于绒毛膜羊膜炎的新生儿患败血症的风险增加。数据库：U30/O30/Term 的 ChIP-seq 数据：GEO GSE81957 U30C/O30C/TermC 的 ChIP-seq 数据：GEO GSE111873 U/L/CU/CL 的 RNA-seq 数据：GEO GSE111927。
