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.
Highlights
Long noncoding RNA are a class of transcripts that are longer than 200 nucleotides without protein coding capacity
When we analyzed the genomic regions separately, such as the promoter, intron and exon regions, the dynamic patterns of long noncoding RNA (lncRNA) genes of demethylation and remethylation were similar to those of protein-coding genes, indicating that the dynamic changes in DNA methylation are in general universal in the two types of genes during human pre-implantation embryonic development (PED) (Figure 1C and Supplementary Figure 1)
We found that the methylation levels in promoter of the lncRNA genes were always higher than that of protein-coding genes during human PED (Figure 1C, 1D and Supplementary Figure 2), suggesting that there exists differential methylation pattern between lncRNA and protein-coding genes
Summary
Long noncoding RNA (lncRNA) are a class of transcripts that are longer than 200 nucleotides without protein coding capacity. LncRNA genes can be classified into intergenic and intragenic, according to their genome localization. Though the molecular basis of the function of many lncRNA genes is just emerging, the recent work indicates their intricate roles in various biological processes, such as X chromosome inactivation [1], imprinting [2], Hox-associated pattern formation [3, 4], neuronal fate specification [5], pluripotency and differentiation control [6,7,8], cell apoptosis and cell cycle control [9, 10], immune response [11, 12], and mitochondria regulation [13]. Most lncRNA genes are transcribed by RNA pol II and have typical hallmarks of pol II transcribed products like 5’ Cap and poly A tail [14]. The expression of both lncRNA and protein-coding genes mediated by pol II can be regulated by DNA methylation alterations [15]
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