H3K9 Methyltransferases Suv39h1 and Suv39h2 Control the Differentiation of Neural Progenitor Cells in the Adult Hippocampus

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dc.contributor.authorGuerra, M.
dc.contributor.authorCáceres, M.
dc.contributor.authorHerrera-Soto, A.
dc.contributor.authorArredondo, S.
dc.contributor.authorVaras-Godoy, M.
dc.contributor.authorvan Zundert, B.
dc.contributor.authorVarela-Nallar, L.
dc.date.accessioned2022-08-12T15:51:59Z
dc.date.available2022-08-12T15:51:59Z
dc.date.issued2022-01
dc.descriptionIndexación: Scopus.es
dc.description.abstractIn the dentate gyrus of the adult hippocampus new neurons are generated from neural precursor cells through different stages including proliferation and differentiation of neural progenitor cells and maturation of newborn neurons. These stages are controlled by the expression of specific transcription factors and epigenetic mechanisms, which together orchestrate the progression of the neurogenic process. However, little is known about the involvement of histone posttranslational modifications, a crucial epigenetic mechanism in embryonic neurogenesis that regulates fate commitment and neuronal differentiation. During embryonic development, the repressive modification trimethylation of histone H3 on lysine 9 (H3K9me3) contributes to the cellular identity of different cell-types. However, the role of this modification and its H3K9 methyltransferases has not been elucidated in adult hippocampal neurogenesis. We determined that during the stages of neurogenesis in the adult mouse dentate gyrus and in cultured adult hippocampal progenitors (AHPs), there was a dynamic change in the expression and distribution of H3K9me3, being enriched at early stages of the neurogenic process. A similar pattern was observed in the hippocampus for the dimethylation of histone H3 on lysine 9 (H3K9me2), another repressive modification. Among H3K9 methyltransferases, the enzymes Suv39h1 and Suv39h2 exhibited high levels of expression at early stages of neurogenesis and their expression decreased upon differentiation. Pharmacological inhibition of these enzymes by chaetocin in AHPs reduced H3K9me3 and concomitantly decreased neuronal differentiation while increasing proliferation. Moreover, Suv39h1 and Suv39h2 knockdown in newborn cells of the adult mouse dentate gyrus by retrovirus-mediated RNA interference impaired neuronal differentiation of progenitor cells. Our results indicate that H3K9me3 and H3K9 methyltransferases Suv39h1 and Suv39h2 are critically involved in the regulation of adult hippocampal neurogenesis by controlling the differentiation of neural progenitor cells.es
dc.description.urihttps://www.frontiersin.org/articles/10.3389/fcell.2021.778345/full
dc.identifier.citationFrontiers in Cell and Developmental Biology, Volume 912, January 2022, Article number 778345es
dc.identifier.doi10.3389/fcell.2021.778345
dc.identifier.issn2296-634X
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/23527
dc.language.isoenes
dc.publisherFrontiers Media S.A.es
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://www.frontiersin.org/about/open-access
dc.subjectadult neurogenesises
dc.subjectdifferentiationes
dc.subjectepigeneticses
dc.subjectH3K9me3es
dc.subjectSuv39h1es
dc.subjectSuv39h2es
dc.titleH3K9 Methyltransferases Suv39h1 and Suv39h2 Control the Differentiation of Neural Progenitor Cells in the Adult Hippocampuses
dc.typeArtículoes
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