Table 1

Summary of characterized functional roles of the CoREST family in neurodevelopment

	CoREST protein involved	Functional role	Species	References
Regulation of pluripotency	CoREST2	Rcor2 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 cells	Mouse and human	Yang et al. (2011)
Regulation of pluripotency	CoREST3	RCOR3 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 region	Chicken	Jung et al. (2018)
Regulation of neuronal differentiation and maturation	CoREST1	Rcor1 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 lineages	Mouse	Fuentes et al. (2012)
	CoREST2	Rcor2 conditional knock-out (Rcor2^cko) mice had significantly reduced brain sizes, cortical thickness, and structural abnormalities of the brain layers; Rcor2^cko 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 pathway	Mouse	Wang et al. (2016)
	CoREST1 and CoREST2	The 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 1	Mouse	Monaghan et al. (2017)
Regulation of neuroinflammation	CoREST1	CoREST1 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 response	Human	Gómez et al. (2008)
Regulation of neuroinflammation	CoREST2	Rcor2 expression was shown to decrease in an aging mouse model, accompanied by an increase in proinflammatory markers; Rcor2 knock-down further increased inflammatory marker expression	Mouse	Alvarez-López et al. (2014)