Marakulina, D. | Search bioRxiv

bioRxiv2025

Functional characterization of DNAAF3-AS1 in chromatin remodeling and H3K36me3 distribution

Long non-coding RNAs (lncRNAs) represent a diversity of transcripts that can regulate gene expression and chromatin remodelling. DNAAF3-AS1 is an lncRNA with a strong genome-wide correlation between DNAAF3-AS1 expression and the histone mark H3K36me3, according to the HiMoRNA database. To validate this association, we performed DNAAF3-AS1 knockdown in human dermal fibroblasts using antisense oligonucleotides following H3K36me3 ChIP-seq. Our results demonstrate that DNAAF3-AS1 depletion leads to a significant redistribution of H3K36me3, with increased signal in intergenic regions and the first exon, and reduced enrichment across gene bodies. Additionally, differential expression analysis revealed that DNAAF3-AS1 knockdown induces promoter switching, with downregulation of gene-body promoters downstream of TSS. These findings establish DNAAF3-AS1 as a potential regulator of H3K36me3 deposition and transcriptional architecture, providing mechanistic insight into lncRNA-mediated epigenetic control.

cell biology↗

bioRxiv2024

HiMoRNA and RNA-Chrom integration: Chromatin-Associated LncRNAs in Genome-Wide Epigenetic Regulation

Long non-coding RNAs (lncRNAs) significantly contribute to genome structure and regulation. Many lncRNAs are known to interact with chromatin and in this way to affect gene expression patterns through epigenetic regulation. Still, experimental protocols for lncRNA-chromatin interactions do not provide any insight into the mechanisms of lncRNA-based genome-wide regulation. Here we present an integration of HiMoRNA - a resource containing correlated lncRNA-epigenetic changes in specific genomic locations genome-wide, - and RNA-Chrom, a resource featuring uniformly processed experimental data on RNA-chromatin interactions. Our integration approach allows generating interpretable and experimentally supported hypotheses on the mechanisms of lncRNA epigenetic regulation of gene expression. For this integration we have tailored the interface of HiMoRNA such that for many lncRNAs experimentally detected RNA-chromatin contacts are available from RNA-Chrom for browsing, analysis and downloading. HiMoRNA peaks supported by RNA-Chrom contacts can be explained by external experimental data. We believe that the integration of HiMoRNA and RNA-Chrom is a convenient and valuable approach that can provide experimental and mechanistic insights and greatly facilitate functional annotation of lncRNAs.

bioinformatics↗