DNA methylation signature of long noncoding RNA genes during human pre-implantation embryonic development

Abstract

DNA methylation have crucial roles in regulating the expression of developmental genes during mammalian pre-implantation embryonic development (PED). However, the DNA methylation dynamic pattern of long noncoding RNA (lncRNA) genes, one type of epigenetic regulators, in human PED have not yet been demonstrated. Here, we performed a comprehensive analysis of lncRNA genes in human PED based on public reduced representation bisulphite sequencing (RRBS) data. We observed that both lncRNA and protein-coding genes complete the major demethylation wave at the 2-cell stage, whereas the promoters of lncRNA genes show higher methylation level than protein-coding genes during PED. Similar methylation distribution was observed across the transcription start sites (TSS) of lncRNA and protein-coding genes, contrary to previous observations in tissues. Besides, not only the gamete-specific differentially methylated regions (G-DMRs) but also the embryonic developmental-specific DMRs (D-DMRs) showed more paternal bias, especially in promoter regions in lncRNA genes. Moreover, coding-non-coding gene co-expression network analysis of genes containing D-DMRs suggested that lncRNA genes involved in PED are associated with gene expression regulation through several means, such as mRNA splicing, translational regulation and mRNA catabolic. This firstly provides study provides the methylation profiles of lncRNA genes in human PED and improves the understanding of lncRNA genes involvement in human PED.