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Epigenetic silencing of the osteoblast-lineage gene program during hippocampal maturation.
Aguilar, Rodrigo; Bustos, Fernando J; Nardocci, Gino; van Zundert, Brigitte; Montecino, Martin.
Afiliação
  • Aguilar R; Faculty of Medicine and Faculty of Life Sciences, Institute of Biomedical Sciences, Universidad Andres Bello, Santiago, Chile.
  • Bustos FJ; FONDAP Center for Genome Regulation, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Nardocci G; Faculty of Medicine and Faculty of Life Sciences, Institute of Biomedical Sciences, Universidad Andres Bello, Santiago, Chile.
  • van Zundert B; Faculty of Medicine and Faculty of Life Sciences, Institute of Biomedical Sciences, Universidad Andres Bello, Santiago, Chile.
  • Montecino M; Faculty of Medicine and Faculty of Life Sciences, Institute of Biomedical Sciences, Universidad Andres Bello, Santiago, Chile.
J Cell Biochem ; 122(3-4): 367-384, 2021 04.
Article em En | MEDLINE | ID: mdl-33135214
Accumulating evidence indicates that epigenetic control of gene expression plays a significant role during cell lineage commitment and subsequent cell fate maintenance. Here, we assess epigenetic mechanisms operating in the rat brain that mediate silencing of genes that are expressed during early and late stages of osteogenesis. We report that repression of the osteoblast master regulator Sp7 in embryonic (E18) hippocampus is mainly mediated through the Polycomb complex PRC2 and its enzymatic product H3K27me3. During early postnatal (P10), juvenile (P30), and adult (P90) hippocampal stages, the repressive H3K27me3 mark is progressively replaced by nucleosome enrichment and increased CpG DNA methylation at the Sp7 gene promoter. In contrast, silencing of the late bone phenotypic Bglap gene in the hippocampus is PRC2-independent and accompanied by strong CpG methylation from E18 through postnatal and adult stages. Forced ectopic expression of the primary master regulator of osteogenesis Runx2 in embryonic hippocampal neurons activates the expression of its downstream target Sp7 gene. Moreover, transcriptomic analyses show that several genes associated with the mesenchymal-osteogenic lineages are transcriptionally activated in these hippocampal cells that express Runx2 and Sp7. This effect is accompanied by a loss in neuronal properties, including a significant reduction in secondary processes at the dendritic arbor and reduced expression of critical postsynaptic genes like PSD95. Together, our results reveal a developmental progression in epigenetic control mechanisms that repress the expression of the osteogenic program in hippocampal neurons at embryonic, postnatal, and adult stages.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoblastos / Fatores de Transcrição / Regiões Promotoras Genéticas / Epigênese Genética / Subunidade alfa 1 de Fator de Ligação ao Core / Hipocampo Limite: Animals Idioma: En Revista: J Cell Biochem Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Chile

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoblastos / Fatores de Transcrição / Regiões Promotoras Genéticas / Epigênese Genética / Subunidade alfa 1 de Fator de Ligação ao Core / Hipocampo Limite: Animals Idioma: En Revista: J Cell Biochem Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Chile