Genome-wide identification of vitamin D receptor–regulated enhancer RNAs reveals epigenetic regulation of CYP24A1 transcription

Among these, eRNAs located at the CYP24A1 locus were robustly induced by VD and correlated with strong transcriptional activation of the gene. Functional analyses using BET inhibition and LNA-mediated knockdown demonstrated that these eRNAs contribute to VD-dependent transcription. Furthermore, CRISPR/dCas9-mediated induction of specific eRNAs enhanced CYP24A1 expression, supporting a direct regulatory role.

In contrast, newly identified target genes such as DLX2 and SYT8 exhibited modest, cell type–dependent responses to VD. Our findings reveal that VDR-mediated gene regulation involves a limited but functionally significant set of eRNAs, particularly at super-enhancer regions, and highlight a unique epigenetic mechanism underlying VD action.