Ezh2-dependent H3K27me3 modification dynamically regulates vitamin D3-dependent epigenetic control of CYP24A1 gene expression in osteoblastic cells

Daniel Moena, Gino Nardocci, Elvis Acevedo, Jane Lian, Gary Stein, Janet Stein, Martin Montecino

Research output: Contribution to journalArticle

Abstract

Epigenetic control is critical for the regulation of gene transcription in mammalian cells. Among the most important epigenetic mechanisms are those associated with posttranslational modifications of chromosomal histone proteins, which modulate chromatin structure and increased accessibility of promoter regulatory elements for competency to support transcription. A critical histone mark is trimethylation of histone H3 at lysine residue 27 (H3K27me3), which is mediated by Ezh2, the catalytic subunit of the polycomb group complex PRC2 to repress transcription. Treatment of cells with the active vitamin D metabolite 1,25(OH)2D3, results in transcriptional activation of the CYP24A1 gene, which encodes a 24-hydroxylase enzyme, that is, essential for physiological control of vitamin D3 levels. We report that the Ezh2-mediated deposition of H3K27me3 at the CYP24A1 gene promoter is a requisite regulatory component during transcriptional silencing of this gene in osteoblastic cells in the absence of 1,25(OH)2D3. 1,25(OH)2D3 dependent transcriptional activation of the CYP24A1 gene is accompanied by a rapid release of Ezh2 from the promoter, together with the binding of the H3K27me3-specific demethylase Utx/Kdm6a and thereby subsequent erasing of the H3K27me3 mark. Importantly, we find that these changes in H3K27me3 enrichment at the CYP24A1 gene promoter are highly dynamic, as this modification is rapidly reacquired following the withdrawal of 1,25(OH)2D3.

Original languageEnglish
Pages (from-to)5404-5412
Number of pages9
JournalJournal of Cellular Physiology
Volume235
Issue number6
DOIs
Publication statusPublished - 7 Jan 2020

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Keywords

  • epigenetic control of transcription
  • osteoblast gene transcription
  • vitamin D-mediated transcription

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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