Polycomb PRC2 complex mediates epigenetic silencing of a critical osteogenic master regulator in the hippocampus

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dc.contributor.authorAguilar, Rodrigo
dc.contributor.authorBustos, Fernando J.
dc.contributor.authorSaez, Mauricio
dc.contributor.authorRojas, Adriana
dc.contributor.authorAllende, Miguel L.
dc.contributor.authorvan Wijnen, Andre J.
dc.contributor.authorvan Zundert, Brigitte
dc.contributor.authorMontecino, Martin
dc.date.accessioned2023-10-03T22:05:27Z
dc.date.available2023-10-03T22:05:27Z
dc.date.issued2016-08
dc.descriptionIndexación: Scopus.es
dc.description.abstractDuring hippocampal neuron differentiation, the expression of critical inducers of non-neuronal cell lineages must be efficiently silenced. Runx2 transcription factor is the master regulator of mesenchymal cells responsible for intramembranous osteoblast differentiation and formation of the craniofacial bone tissue that surrounds and protects the central nervous system (CNS) in mammalian embryos. The molecular mechanisms that mediate silencing of the Runx2 gene and its downstream target osteogenic-related genes in neuronal cells have not been explored. Here, we assess the epigenetic mechanisms that mediate silencing of osteoblast-specific genes in CNS neurons. In particular, we address the contribution of histone epigenetic marks and histone modifiers on the silencing of the Runx2/p57 bone-related isoform in rat hippocampal tissues at embryonic to adult stages. Our results indicate enrichment of repressive chromatin histone marks and of the Polycomb PRC2 complex at the Runx2/p57 promoter region. Knockdown of PRC2 H3K27-methyltransferases Ezh2 and Ezh1, or forced expres sion of the Trithorax/COMPASS subunit Wdr5 activates Runx2/p57 mRNA expression in both immature and mature hippocampal cells. Together these results indicate that complementary epigenetic mechanisms progressively and efficiently silence critical osteoblastic genes during hippocampal neuron differentiation. © 2016 Elsevier B.V. All rights reserved.es
dc.description.abstractAcknowledgements This work was supported by grants from FONDAP 15090007 (to M.M. and M.L.A.), FONDECYT 1130706 (to M.M.), FONDECYT 3150694 (to MS) and FONDECYT 1140301 (to B.vZ.). Additional funding was pro vided by NIH (R01 AR049069 to A.J.vW.). R.A. and F.B. were supported by Doctoral Fellowships from CONICYT, Chile. A.R. was partially funded by Doctoral Fellowships from COLCIENCIAS and Pontificia Universidad Javeriana, Colombia.
dc.description.urihttps://www-sciencedirect-com.recursosbiblioteca.unab.cl/science/article/pii/S1874939916300992?via%3Dihub
dc.identifier.citationBiochimica et Biophysica Acta - Gene Regulatory Mechanisms. Volume 1859, Issue 8, Pages 1043 - 1055. 1 August 2016es
dc.identifier.doi10.1016/j.bbagrm.2016.05.009
dc.identifier.issn1874-9399
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/53406
dc.language.isoenes
dc.publisherElsevier B.V.es
dc.subjectRunx2es
dc.subjectEpigenetic Regulation of Gene Expressiones
dc.subjectHippocampuses
dc.titlePolycomb PRC2 complex mediates epigenetic silencing of a critical osteogenic master regulator in the hippocampuses
dc.typeArtículoes
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