Scholarlink

<p>Vitamin D (VD) exerts diverse physiological effects primarily through the vitamin D receptor (VDR), a ligand-dependent transcription factor. Given the broad spectrum of VD actions, presence of uncharacterized target genes regulated by VD is likely. In this study, we performed a comprehensive genome-wide analysis to identify enhancer RNAs (eRNAs) involved in VD-dependent gene regulation. Using integrated ChIP-seq, RNA-seq, and NET-CAGE analyses in human HCT116 and HaCaT cells, we mapped VDR-binding sites and identified VD target transcripts. VDR binding was strongly dependent on 1,25(OH)<sub>2</sub>D<sub>3</sub> and predominantly localized to enhancer regions marked by H3K27ac, indicating its association with active chromatin. Using stepwise filtering, we identified a limited number of high-confidence eRNA candidates associated with VDR-bound regulatory regions. Among these, eRNAs located at the CYP24A1 locus were robustly induced by VD and were correlated with strong transcriptional activation of the gene. Functional analyses using inhibition of bromodomain and extraterminal proteins and locked nucleic acid-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. Our findings reveal that VDR-mediated gene regulation involves a limited but functionally significant set of eRNAs, particularly in super-enhancer regions, and highlight a unique epigenetic mechanism underlying VD action.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月5日

查看全文
  • Takahiro Sawada,
  • Kouki Nojiri,
  • Kaoru Yamagata,
  • Ngo Thi Uyen,
  • Tram Thi-Ngoc Nguyen,
  • Yoshiya Tanaka,
  • Shingo Nakayamada,
  • Yoshiaki Kanemoto,
  • Tomohiro Kurokawa,
  • Shigeaki Kato

摘要

Vitamin D (VD) exerts diverse physiological effects primarily through the vitamin D receptor (VDR), a ligand-dependent transcription factor. Given the broad spectrum of VD actions, presence of uncharacterized target genes regulated by VD is likely. In this study, we performed a comprehensive genome-wide analysis to identify enhancer RNAs (eRNAs) involved in VD-dependent gene regulation. Using integrated ChIP-seq, RNA-seq, and NET-CAGE analyses in human HCT116 and HaCaT cells, we mapped VDR-binding sites and identified VD target transcripts. VDR binding was strongly dependent on 1,25(OH)2D3 and predominantly localized to enhancer regions marked by H3K27ac, indicating its association with active chromatin. Using stepwise filtering, we identified a limited number of high-confidence eRNA candidates associated with VDR-bound regulatory regions. Among these, eRNAs located at the CYP24A1 locus were robustly induced by VD and were correlated with strong transcriptional activation of the gene. Functional analyses using inhibition of bromodomain and extraterminal proteins and locked nucleic acid-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. Our findings reveal that VDR-mediated gene regulation involves a limited but functionally significant set of eRNAs, particularly in super-enhancer regions, and highlight a unique epigenetic mechanism underlying VD action.