Abstract
More than 98% of the human genome does not encode proteins, and the vast majority of the noncoding regions have not been well studied. Some of these regions contain enhancers and functional non-coding RNAs. Previous research suggested that enhancer transcripts could be potent independent indicators of enhancer activity, and some enhancer lncRNAs (elncRNAs) have been proven to play critical roles in gene regulation. Here, we identified enhancer–promoter interactions from high-throughput chromosome conformation capture (Hi-C) data. We found that elncRNAs were highly enriched surrounding chromatin loop anchors. Additionally, the interaction frequency of elncRNA-associated enhancer–promoter pairs was significantly higher than the interaction frequency of other enhancer–promoter pairs, suggesting that elncRNAs may reinforce the interactions between enhancers and promoters. We also found that elncRNA expression levels were positively correlated with the interaction frequency of enhancer–promoter pairs. The promoters interacting with elncRNA-associated enhancers were rich in RNA polymerase II and YY1 transcription factor binding sites. We clustered enhancer–promoter pairs into different groups to reflect the different ways in which elncRNAs could influence enhancer–promoter pairs. Interestingly, G-quadruplexes were found to potentially mediate some enhancer–promoter interaction pairs, and the interaction frequency of these pairs was significantly higher than that of other enhancer–promoter pairs. We also found that the G-quadruplexes on enhancers were highly related to the expression of elncRNAs. G-quadruplexes located in the promoters of elncRNAs led to high expression of elncRNAs, whereas G-quadruplexes located in the gene bodies of elncRNAs generally resulted in low expression of elncRNAs.
Highlights
It has been widely accepted that a large proportion of the human genome is transcribed, but that less than 2% of the transcripts are subsequently translated into proteins (Katayama et al, 2005; Djebali et al, 2012; Sallam et al, 2018)
We found that chromatin loops and enhancer–promoter interactions were highly associated with elncRNAs
ElncRNAs Are Highly Enriched in Chromatin Loop Anchors
Summary
It has been widely accepted that a large proportion of the human genome is transcribed, but that less than 2% of the transcripts are subsequently translated into proteins (Katayama et al, 2005; Djebali et al, 2012; Sallam et al, 2018). Iyer et al identified 58,648 lncRNA genes in the human genome, of which 1% harbored ultraconserved elements and 7% overlapped with disease-associated SNPs (Iyer et al, 2015). Some lncRNAs can regulate the expression of neighboring (cis) or distal (trans) genes (Yu et al, 2018). In cis means that lncRNAs regulate target genes by the act of transcription (Tehrani et al, 2018). In addition to acting in cis, some lncRNAs translocate from their sites of synthesis and regulate distal target genes in trans (Kopp and Mendell, 2018). The Xist lncRNA participates in silencing transcription in trans by interacting with SHARP (McHugh et al, 2015)
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