Table 1

Summary of characterized functional roles of the CoREST family in neurodevelopment

CoREST protein involvedFunctional roleSpeciesReferences
Regulation of pluripotencyCoREST2Rcor2 knock-down resulted in reduced proliferation and impaired pluripotency; the overexpression of CoREST2, together with Oct3/4, Klf4, c-Myc, was successfully used to replace Sox2 in the generation of mouse and human induced pluripotent stem cellsMouse and human Yang et al. (2011)
CoREST3RCOR3 knock-down resulted in significant upregulation of NANOG and enriched acetylated H3K9 residue on the REST binding site in the NANOG promoter region; indicating CoREST3 regulates NANOG expression through the formation of a complex with REST and the deacetylation of the NANOG promoter regionChicken Jung et al. (2018)
Regulation of neuronal differentiation and maturationCoREST1Rcor1 knock-down resulted in impaired radial migration of cortical pyramidal neurons in the developing cerebral cortex; Rcor1 knock-down cells exhibited delayed migration, remained in the ventricular zone and expressed Sox2 and Tbr2, suggesting the cells had not differentiated from precursor lineagesMouse Fuentes et al. (2012)
CoREST2Rcor2 conditional knock-out (Rcor2cko) mice had significantly reduced brain sizes, cortical thickness, and structural abnormalities of the brain layers; Rcor2cko mice had reduced numbers of neuronal progenitors and neurons, and increased cell death; the gene knock-out (KO) mice showed significant upregulation of ventral markers and decrease in cortical markers, suggesting CoREST2 regulates the sonic hedgehog signaling pathwayMouse Wang et al. (2016)
CoREST1 and CoREST2The individual gene knock-out (KO) mice were indistinguishable to the control cohort, combined deletion resulted in severe brain phenotypes and death; Rcor1/2 KO mice had an increased population of proliferating cells, suggesting these mice lacked the mechanism to differentiate precursors into postmitotic neurons and mature oligodendrocytes; CoREST1 and CoREST2 are hypothesized to elicit this function through the formation of a complex with insulinoma-associated 1Mouse Monaghan et al. (2017)
Regulation of neuroinflammationCoREST1CoREST1 interacts with the promoter of hsp70, a gene that encodes heat shock protein 70 (Hsp70); through this interaction, CoREST1 represses both HSF1-dependent and heat-shock-dependent transcriptional activation of hsp70; RCOR1 knock-down resulted in loss of Hsp70 repression, inducing the heat shock responseHuman Gómez et al. (2008)
CoREST2Rcor2 expression was shown to decrease in an aging mouse model, accompanied by an increase in proinflammatory markers; Rcor2 knock-down further increased inflammatory marker expressionMouse Alvarez-López et al. (2014)