RGD Reference Report - Ezh2-dependent H3K27me3 modification dynamically regulates vitamin D3-dependent epigenetic control of CYP24A1 gene expression in osteoblastic cells. - Rat Genome Database

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

Authors: Moena, Daniel  Nardocci, Gino  Acevedo, Elvis  Lian, Jane  Stein, Gary  Stein, Janet  Montecino, Martin 
Citation: Moena D, etal., J Cell Physiol. 2020 Jun;235(6):5404-5412. doi: 10.1002/jcp.29428. Epub 2020 Jan 7.
RGD ID: 151665135
Pubmed: PMID:31907922   (View Abstract at PubMed)
PMCID: PMC7056562   (View Article at PubMed Central)
DOI: DOI:10.1002/jcp.29428   (Journal Full-text)

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)2 D3 , 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)2 D3 . 1,25(OH)2 D3 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)2 D3 .

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to vitamin D  IDA 151665135 RGD 
positive regulation of transcription by RNA polymerase II  IMP 151665135 RGD 
protein modification process  IMP 151665135histone H3-K27 demethylationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Kdm6a  (lysine demethylase 6A)


Additional Information