Transcriptomic and ChIP-seq Integrative Analysis Reveals Important Roles of Epigenetically Regulated lncRNAs in Placental Development in Meishan Pigs

The development of the placental fold, which increases the maternal–fetal interacting surface area, is of primary importance for the growth of the fetus throughout the whole pregnancy. However, the mechanisms involved remain to be fully elucidated. Increasing evidence has revealed that long non-coding RNAs (lncRNAs) are a new class of RNAs with regulatory functions and could be epigenetically regulated by histone modifications. In this study, 141 lncRNAs (including 73 up-regulated and 68 down-regulated lncRNAs) were identified to be differentially expressed in the placentas of pigs during the establishment and expanding stages of placental fold development. The differentially expressed lncRNAs and genes (DElncRNA-DEgene) co-expression network analysis revealed that these differentially expressed lncRNAs (DElncRNAs) were mainly enriched in pathways of cell adhesion, cytoskeleton organization, epithelial cell differentiation and angiogenesis, indicating that the DElncRNAs are related to the major events that occur during placental fold development. In addition, we integrated the RNA-seq (RNA sequencing) data with the ChIP-seq (chromatin immunoprecipitation sequencing) data of H3K4me3/H3K27ac produced from the placental samples of pigs from the two stages (gestational days 50 and 95). The analysis revealed that the changes in H3K4me3 and/or H3K27ac levels were significantly associated with the changes in the expression levels of 37 DElncRNAs. Furthermore, several H3K4me3/H3K27ac-lncRNAs were characterized to be significantly correlated with genes functionally related to placental development. Thus, this study provides new insights into understanding the mechanisms for the placental development of pigs.