Integration of HiMoRNA and RNAChrom: Validation of the Functional Role of Long Non-coding RNAs in the Epigenetic Regulation of Human Genes Using RNA-Chromatin Interactome Data.

Long non-coding RNAs (lncRNAs) play a crucial role in the epigenetic regulation of gene expression by recruiting chromatin-modifying proteins to specific genomic loci. Two databases, previously developed by our groups, HiMoRNA and RNA-Chrom, provide valuable insights into this process. The former contains data on epigenetic modification regions (peaks) correlated with lncRNA expression, while the latter offers genome-wide RNA-chromatin interaction data for tens of thousands of RNAs. This study integrated the two resources to generate experimentally supported, interpretable hypotheses regarding lncRNA-mediated epigenetic gene expression regulation. We adapted the web interfaces of HiMoRNA and RNA-Chrom to enable the retrieval of chromatin contacts for each "lncRNA-pigenetic modification-ssociated gene" triad from HiMoRNA, either at specific genomic loci or genome-wide via RNA-Chrom. The integration analysis revealed that for the lncRNAs MALAT1, HOXC-AS2, NEAT1, NR2F1-AS1, PVT1, and MEG3, most HiMoRNA peaks are located within 25 kb of their RNA-Chrom contacts. Further investigation confirmed the RNA-hromatin contacts of MIR31HG and PVT1 lncRNAs, with HiMoRNA peaks for H3K27ac and H3K27me3 marks in the loci of the genes and , respectively, which are known to be regulated by these RNAs. Thus, the integration of HiMoRNA and RNA-Chrom offers a powerful platform to elucidate the role of specific lncRNAs in the regulation of histone modifications at both individual loci and genome-wide levels. We expect this integration to help significantly advance the functional annotation of human lncRNAs.