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

TL;DR

This paper integrates two databases to better understand how long non-coding RNAs regulate gene expression through chromatin interactions.

Contribution

The novel integration of HiMoRNA and RNA-Chrom databases enables experimentally supported hypotheses on lncRNA-mediated epigenetic regulation.

Findings

Most HiMoRNA peaks for specific lncRNAs are within 25 kb of RNA-Chrom contacts.

RNA–chromatin contacts of MIR31HG and PVT1 lncRNAs were confirmed with histone modification marks at GLI2 and LATS2 genes.

The integration provides a platform to study lncRNA roles in histone modification regulation at individual and genome-wide levels.

Abstract

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 GLI2 and
LATS2, 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.

Figures