Epigenetic silencing of the osteoblast-lineage gene program during hippocampal maturation

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dc.contributor.authorAguilar, Rodrigo
dc.contributor.authorBustos, Fernando J.
dc.contributor.authorNardocci, Gino
dc.contributor.authorvan Zundert, Brigitte
dc.contributor.authorMontecino, Martin
dc.date.accessioned2025-01-20T23:56:03Z
dc.date.available2025-01-20T23:56:03Z
dc.date.issued2021
dc.description.abstractAccumulating 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.
dc.fuente.origenWOS
dc.identifier.doi10.1002/jcb.29865
dc.identifier.eissn1097-4644
dc.identifier.issn0730-2312
dc.identifier.urihttps://doi.org/10.1002/jcb.29865
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/95129
dc.identifier.wosidWOS:000583241800001
dc.issue.numero3-4
dc.language.isoen
dc.pagina.final384
dc.pagina.inicio367
dc.revistaJournal of cellular biochemistry
dc.rightsacceso restringido
dc.subjectepigenetic control of gene transcription
dc.subjectsilencing of non&#8208
dc.subjectneural genes in hippocampal cells
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleEpigenetic silencing of the osteoblast-lineage gene program during hippocampal maturation
dc.typeartículo
dc.volumen122
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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