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

Budkina, A.; Zubritskiy, A.; Aneke, J.; Marakulina, D.; Medvedeva, Y. A.

2025-12-16 cell biology
10.64898/2025.12.15.694275 bioRxiv
Show abstract

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.

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