Decreased Expression of CoREST1 and CoREST2 Together with LSD1 and HDAC1/2 during Neuronal Differentiation

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Liste des auteurs: Saez JE, Gomez AV, Barrios AP, Parada GE, Galdames L, Gonzalez M
Editeur: Public Library of Science
Année de publication: 2015
Journal: PLoS ONE (1932-6203)
Numéro du volume: 10
Numéro de publication: 6
Page d'accueil: e0133555
Nombre de pages: 2
ISSN: 1932-6203
eISSN: 1932-6203
Languages: Anglais-Royaume-Uni (EN-GB)


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.




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