. 2021 Jan 15;11(1):62. doi: 10.3390/life11010062

Table 1.

List of epigenetic marks and their roles during OPC specification.

DNA Modification	Enzyme/Mark	Role	Targeted Genes or Functions	Model	Methods	References
DNA methylation		Negative role in NSCs differentiation to glia	Repression of astrogliogenesis (Stat3 binding element in Gfap promoter)	In vitro neuroepithelial cells	BS PCR on neuroepithelial cells	Takizawa et al. [85]
	DNMT1	Negative role in NPCs differentiation to glia	Control of the timing of astrogliogenesis by repression of astrocyte-specific genes (Gfap, Stat1)	Nestin-cre;Dnmt1flox NPCs	BS PCR on Nestin-cre;Dnmt1flox NPCs	Fan et al. [86]
		Positive role in NSCs differentiation to glia	Repression of neuron-specific genes (Dlx1, Dlx2, Trb1)	Sox2-EGFP mice	WGBS on NS/PCs from Sox2-EGFP transgenic mice	Sanosaka et al. [84]
	DNMT1	Positive role in NSCs specification to OPCs	Repression of neuron-specific (Ndrg4, Camk1, Ephb2) and astrocyte-specific (Aldh1l1, Pax6, Rfx4) genes	Olig1cre;Dnmt1flox mice	RNA-Seq and ERRBS on sorted neonatal OPCs and OLs, RNA-Seq on sorted Olig1cre;Dnmt1flox OPCs	Moyon et al. [91]
DNA demethylation		Positive role in ESCs transition to NSCs	Activation of transcription factors (Sox2, Sox21, Ascl1)	Sox2-EGFP mice	WGBS on NS/PCs from Sox2-EGFP transgenic mice	Sanosaka et al. [84]
		Positive role in NSCs differentiation to glia	Activation of gliogenic promoters (NFI, Tcf3, Gfap, Kcnj10, Sox8)	Sox2-EGFP mice	WGBS on NS/PCs from Sox2-EGFP transgenic mice	Sanosaka et al. [84]
		Positive role in NSCs differentiation to glia	Activation of gliogenic promoters (Stat3 binding site in Gfap promoter, Aldoc)	In vitro NPCs and astrocytes from mice	MIAMI and BS on NPCs and astrocytes	Hatada et al. [87]
DNA hydroxymethylation	TET1	Positive role in NSCs differentiation to OPCs	Activation of OL genes (Olig1, Sox10, Id2/4)	Olig1cre;Tet1flox mice	hMeDIP-Seq on in vitro neonatal NSCs and OPCs, RNA-Seq on in vitro Olig1cre;Tet1flox OPCs	Zhang et al. [92]
*Histone Modification*	*Enzyme/Mark*	*Role*	*Targeted Genes or Functions*	*Model*	*Methods*	*References*
Histone methylation	PRC2 (EZH2) (H3K27me3)	Positive role in NSCs differentiation to OPCs		In vitro primary cultures + Olineu + Ezh2 expression vector/shRNA		Sher et al. [94]
	PRC2 (EZH2) (H3K27me3)	Positive role in NSCs differentiation to OPCs	Repression of neuronal (NeuroD2, Tlx3), astrocytic (Tal1), OL (Olig2, Pdgfra, Nkx2.2) genes	In vitro NSCs and OPCs + shRNA	ChIP-Seq on in vitro NSCs and OLs	Sher et al. [95]
	PRC2 (EED) (H3K27me3)	Positive role in astrocyte–OPC fate switch		Olig1cre;Eedflox and PdgfracreRT;Eedflox mice		Wang et al. [96]
	H3K27me3	Positive role in NSCs differentiation to OPCs	Repression of global lineage alternative choice	In vitro OPCs; Cnp-EGFP mice	ChIP-Seq on in vitro OPCs and OLs (H3K27me3)	Liu et al. [97]
	PRMT1	Positive role in NSCs differentiation to OPCs		Nestin-cre;Prmt1flox mice		Hashimoto et al. [98]
Histone (de)acetylation	CBP (H3K9/K14ac)	Positive role in NSCs differentiation	Sequential activation of promoters of neuronal (Tuba1a), astrocytes (Gfap), OL (Mbp)	In vitro cortical precursors + siRNA/inhibitors; cbp+/− mice	ChIP-qPCR on cbp+/− cortices	Wang et al. [99]
	HDACs	Positive role in oligodendrogenesis		In vivo HDAC inhibition in rats		Liu et al. [100]
	HDAC1/HDAC2	Positive role in Shh-induced oligodendrogenesis	Repression of genes associated with Notch signaling (Hey1, Hey2) and Wnt signaling (Tbx3)	In vitro OPCs, Olineu cells + shRNA/inhibitors	ChIP on in vitro Olineu and GeneChip on in vitro OPCs	Wu et al. [101]
	HDAC2 (H3K9deac)	Negative role in NSCs differentiation to OPCs	Repression of oligodendroglial differentiation genes (Sox10) in the presence of thyroid hormone	In vitro NSCs, Olineu, OPCs + siRNA/inhibitors	ChIP-Seq on in vitro NSCs	Castelo-Branco et al. [102]
	HDAC3	Positive role in astrocyte–OL fate switch	Activation of enhancers of OPC genes (Olig2, Ng2) and repression of astrogliogeneis genes (Stat3) and neuronal genes (Bdnf)	In vitro astrocytes and OPCs + inhibitors/expression vectors; Olig1Cre;Hdac3flox, PDGFRaCreERT2;Hdac3flox; Syn1Cre;Hdac3flox mice	ChIP-Seq on in vitro OPCs and OL; RNA-Seq on optic nerves from Olig1cre;Hdac3flox mice	Zhang et al. [103]
	SIRT1 (H3K9deac)	Negative role in NSCs differentiation to OPCs	Repression of differentiation to OPCs (deacetylation at the Pdgfrα promoter)	In vitro OPCs, NS/PCs + inhibitors; NestinCre;Sirt1flox mice	ChIP-qPCR on in vitro NS/PCs	Rafalski et al. [104]
*Chromatin Organization*	*Enzyme/Mark*	*Role*	*Targeted Genes or Functions*	*Model*	*Methods*	*References*
Chromatin remodelers	HMGA1, 2	Negative role in NPCs differentiation to glia	Repression of astrogenic transition	In vitro and in vivo NPCs + shRNA/overexpression		Kishi et al. [105]
	HMGB1, 2, 3, 4		Dynamically expressed in NSCs	In vitro NSCs, Nestin-GFP mice, HMGB2−/− mice	IHC, qPCR, shotgun proteomics on in vitro NSCs	Abraham et al. [106]
	HMGB2	Possible role in NSCs proliferation and maintenance		In vitro NSCs, Nestin-GFP mice, HMGB2−/− mice	IHC, qPCR, shotgun proteomics on in vitro NSCs	Abraham et al. [106]
	HMGB2	Role in neuron–glia fate switch		In vitro NS/PCs, HMGB2−/− mice		Bronstein et al. [107]
	HMGB4	Negative role in NSCs differentiation to OPCs	Regulation of neuronal, astrocyte, oligodendrocyte genes (Fabp7, NeuroD1, Gfap, Ppp1r14a)	In vitro neurons, neurospheres and various cell lines + lentivirus; HMGB4 Vivo-Morpholinos	Microarray on HMGB4-EGFP over-expressing HEK 293T cells	Rouhiainen et al. [108]
	HMGN family	Positive role in neuron–glia fate switch	Modulation of the response to gliogenic signals	In vitro NPCs + shRNA/overexpression	qPCR, IHC, BS and microarray on in vitro NPCs	Nagao et al. [109]
	BRG1	Positive role in NSCs maintenance and gliogenesis	Repression of neuronal differentiation in NSCs	In vitro NSCs, NestinCre;Brg1flox mice	IHC; DNA microarray on CNS tissues of NestinCre;Brg1flox mice	Matsumoto et al. [110]
		Positive role in NSCs differentiation to neurons	Activation of neuronal genes (Ngn and NeuroD)	In vitro pluriopotent P19 cells + plasmids, Xenopus + Brg1 morpholino	IHC	Seo at al. [111]
		Limited role in NSCs		zebrafish + Brg1 morpholino	IHC, ISH	Gregg et al. [112]
*Post-Transcriptional Modification*	*Enzyme/Mark*	*Role*	*Targeted Genes or Functions*	*Model*	*Methods*	*References*
Long non-coding RNA	lnc-158	Positive role in NSCs differentiation to OPCs	Activation of OL genes (Cnp, Mbp, Mag, Osp)	In vitro NSCs + lnc-158 overexpression and siRNA		Li et al. [113]
	lnc-OPC	Positive role in NSCs differentiation to OPCs	Activation of OL genes (Mbp, Plp1, Cnp)	NSCs + shRNA	ChIP-Seq and RNA-Seq on in vitro NSCs	Dong et al. [114]
	Neat1	Positive role in NSCs differentiation to OPCs	Activation of OL genes (Olig1, Olig2, Gpr17, Sox8)	Neat1−/− mice	ChIP-Seq on human tissues; RNA-Seq on Neat1−/− mouse brains	Katsel et al. [115]
	Sox8OT	Possible role in NSCs differentiation to OPCs	Via Sox8 activation	Descriptive study		Mercer et al. [116]
MicroRNA	miR-124	Positive role in NSCs differentiation to neurons	Repression of Ezh2 expression	In vitro NSCs + N2a neuroblastoma + P19 cells + overexpression	Microarray on N2a cells	Neo et al. [117]
	miR-153	Negative role in NSCs differentiation to glia	Repression of gliogenic genes (Nfia/b)	In vitro ESCs + shRNA + artifical miRNAs		Tsuyama et al. [118]
	miR-17/106	Positive role in NSCs differentiation to glia	Activation of gliogenesis (p38)	in vitro ESCs and mouse embryos + lentivirus		Naka-Kaneda et al. [119]

BS: bisulfite sequencing, ChIP: chromatin immunoprecipitation, ERRBS: enhanced reduced representation bisulfite sequencing, hMeDIP-Seq: hMeDIP: hydroxyMethylated DNA immunoprecipitation; IHC: immunohistochemistry; ISH: in situ hybridization; NPCs: neural precursor or progenitor cells, NS/PCs: neural stem/progenitor cells; MIAMI: microarray-based integrated analysis of methylation by isoschizomers, qPCR: quantitative polymerase chain reaction; Seq: sequencing, WGBS: whole-genome bisulfite sequencing.