Comprehensive Characterization Of Lincrnas' Functions In Transcription Regulation Through Long-range Chromatin Interactions

LncRNAs are emerging as important regulators of cellular functions,however,the mechanisms for their transcription regulation and functions are not well explored.Here we characterized lincRNAs through long-range chromatin interactions:how the distal regulatory elements regulate the transcription of lincRNAs through long-range chromatin interactions,and how lincRNAs regulate the transcription of protein-coding genes in both DNA and RNA levels.The results showed that lincRNA genes were widely distributed in the functionally organized chromatin interaction networks,and were regulated by distal regulatory elements.Different types of distal regulatory elements had distinct impact on lincRNA genes.LincRNA genes regulated by super-enhancers exhibited higher expression levels and had higher interaction degrees.LincRNA and protein-coding genes were organized into large co-transcriptional framework,in which lincRNAs were more centered.Promoter regions of lincRNAs displayed two distinct patterns of chromatin states:promoters and enhancer-like,indicating different regulatory functions.We combined DNA-DNA interactions data illustrated by ChIA-PET and RNA-DNA interactions data illustrated by CHART,and used two lincRNAs NEAT1 and MALAT1 as examples.The results showed that the chromatin interactions of lincRNAs with other genes suggested a potential mechanism for lincRNAs regulating other genes in RNA level,since the transcribed lincRNAs could conduct their functions at the local spatial regions with other genes.This is a novel way to predict the functions of lincRNAs,and it is more direct than the coexpression-based method.Some lincRNA genes in cell-specific chromatin interaction network showed exclusive expression profiles,which were potentially linked to cell-specific functions.SNPs within lincRNAs,showed that some lincRNAs were disease-associated and the chromatin interactions suggested the potential target genes of these lincRNA-associated SNPs.Our studies provide new insight into the roles lincRNAs play in transcription regulation.