title: Decreased Expression of CoREST1 and CoREST2 Together with LSD1 and HDAC1/2 during Neuronal Differentiation.
abstract: CoREST (CoREST1, rcor1) transcriptional corepressor together with the histone demethylase LSD1 (KDM1A) and the histone deacetylases HDAC1/2 form LSD1-CoREST-HDAC (LCH) transcriptional complexes to regulate gene expression. CoREST1 belong to a family that also comprises CoREST2 (rcor2) and CoREST3 (rcor3). CoREST1 represses the expression of neuronal genes during neuronal differentiation. However, the role of paralogs CoREST2 and CoREST3 in this process is just starting to emerge. Here, we report the expression of all CoRESTs and partners LSD1 and HDAC1/2 in two models of neuronal differentiation: Nerve-Growth-Factor (NGF)-induced neuronal phenotype of PC12 cells, and in vitro maturation of embryonic rat cortical neurons. In both models, a concomitant and gradual decrease of LSD1, HDAC1, HDAC2, CoREST1, and CoREST2, but not CoREST3 was observed. As required by the study, full-length rat rcor1 gene was identified using in silico analysis of available rat genome. The work was also complemented by the analysis of rat RNA-seq databases. The analysis showed that all CoRESTs, including the identified four splicing variants of rat CoREST3, display a wide expression in adult tissues. Moreover, the analysis of RNA-seq databases showed that CoREST2 displays a higher expression than CoREST1 and CoREST3 in the mature brain. Immunofluorescent assays and immunoblots of adult rat brain showed that all CoRESTs are present in both glia and neurons. Regarding functional partnership, CoREST2 and CoREST3 interact with all LSD1 splicing variants. In conclusion, neuronal differentiation is accompanied by decreased expression of all core components of LCH complexes, but not CoREST3. The combination of the differential transcriptional repressor capacity of LCH complexes and variable protein levels of its different components should result in a finely tuned gene expression during neuronal differentiation and in the adult brain.
authors.affiliation: Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Julián Esteban
authors.initials: JE
authors.lastname: Sáez
authors.affiliation: Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Andrea Verónica
authors.initials: AV
authors.lastname: Gómez
authors.affiliation: Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Álvaro Patricio
authors.initials: ÁP
authors.lastname: Barrios
authors.affiliation: Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Guillermo Eduardo
authors.initials: GE
authors.lastname: Parada
authors.affiliation: Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Galdames
authors.affiliation: Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Marcela
authors.initials: M
authors.lastname: González
authors.affiliation: Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: María Estela
authors.initials: ME
authors.lastname: Andrés
mesh_terms: D000818:Animals; D056970:Co-Repressor Proteins / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000235:genetics*; D056464:Histone Deacetylase 2 / Q000235:genetics*; D056466:Histone Demethylases / Q000235:genetics*; D006801:Humans; D008297:Male; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D016716:PC12 Cells; D020033:Protein Isoforms / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D056970:Co-Repressor Proteins; C000588854:CoREST protein, rat; C000607382:CoREST2 protein, rat; D020033:Protein Isoforms; D056466:Histone Demethylases; C557089:KDM1A protein, rat; C515890:Hdac1 protein, rat; C533426:Hdac2 protein, rat; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2