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

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

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

Afiliação

Moena D; Institute of Biomedical Sciences and FONDAP Center for Genome Regulation, Faculty of Medicine and Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile.
Nardocci G; Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Concepcion, Chile.
Acevedo E; Institute of Biomedical Sciences and FONDAP Center for Genome Regulation, Faculty of Medicine and Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile.
Lian J; Institute of Biomedical Sciences and FONDAP Center for Genome Regulation, Faculty of Medicine and Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile.
Stein G; Department of Biochemistry, University of Vermont College of Medicine, Burlington, Vermont.
Stein J; Department of Biochemistry, University of Vermont College of Medicine, Burlington, Vermont.
Montecino M; Department of Biochemistry, University of Vermont College of Medicine, Burlington, Vermont.

J Cell Physiol ; 235(6): 5404-5412, 2020 06.

Article em En | MEDLINE | ID: mdl-31907922

RESUMO

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 .

Assuntos

Colecalciferol/genética; Proteína Potenciadora do Homólogo 2 de Zeste/genética; Osteossarcoma/genética; Vitamina D3 24-Hidroxilase/genética; Animais; Linhagem Celular Tumoral; Epigênese Genética/genética; Regulação da Expressão Gênica no Desenvolvimento/genética; Código das Histonas/genética; Humanos; Osteoblastos/metabolismo; Osteossarcoma/patologia; Regiões Promotoras Genéticas/genética; Processamento de Proteína Pós-Traducional/genética; Ratos; Ativação Transcricional/genética

Palavras-chave

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

Texto completo

Adicionar na Minha BVS

Imprimir

XML

PubMed Links

Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteossarcoma / Colecalciferol / Vitamina D3 24-Hidroxilase / Proteína Potenciadora do Homólogo 2 de Zeste Limite: Animals / Humans Idioma: En Revista: J Cell Physiol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Chile País de publicação: Estados Unidos

Texto completo

Adicionar na Minha BVS

Imprimir

XML

PubMed Links

Buscar no Google