Table 1.

Roles of PRC1, PRC2, G9a, and annotated lncRNAs in the development and function of Th1, Th2, Treg, and Th17 cells.

	Th1	Th2	Treg	Th17
PRC1	Absence of Bmi1 impacts Th1 generation and maintenance (58).	Regulates Th2 differentiation and cytokine expression (59, 60). Overexpression of Bmi-1 increases GATA3 expression and stability (59). Loss of Mel-18 impacts Th2 differentiation in vivo (60).	Maintains Treg signature gene expression (61). Inactivation leads to systemic immune mediated disease (61).	Knockdown of Mel-18 leads to decreased expression of IL17A, IL17F, and RORC (62).
PRC2	Inhibits Th1 differentiation and cytokine production (63, 64). EZH2 deficiency enhances production of Th1 cytokines and increased T-bet expression (63, 64).	Inhibits Th2 differentiation and cytokine production (63, 64). EZH2 deficiency enhances production of Th2 cytokines and increased GATA3 expression (63, 64).	EZH2 is required to promote the FOXP3-mediated gene repression program following TCR stimulation (65). Loss of EZH2 in Tregs in vivo leads to multi-organ inflammation and increases susceptibility to experimental models of autoimmunity (66, 65).	EZH2-deficient naïve CD4+ T cells stimulated under Th17 polarizing conditions displayed enhanced production of IL-17 (63).
G9a	No evidence supports a role for G9a in Th1 biology.	Required for Th2-specific cytokine expression (40). Loss of G9a prevents Th2 differentiation and increases IL-17A expression (40, 42).	Absence of G9a in CD4+ T cells is associated with increased FOXP3 expression (42). G9a expression in CD4+ T cells is necessary for development of colitis in mice (42).	Absence of G9a in CD4+ T cells is associated with increased IL-17A expression in vivo and in vitro (42). Recruited by RelB to silence IL17A locus in mouse model of EAE (67).
LncRNA	Linc-MAF-4 promotes Th1 differentiation through silencing of Th2 transcription factor MAF (49, 68). IFNG-AS1 recruits H3-K4-methyltransferase to Ifng locus and is upregulated in response to Th1-polarizing cytokines (52, 69, 70, 71).	Th2-LCR-lncRNA recruits WDR5-containing complexes to Th2-specific cytokine loci facilitating their expression (72). LincR-CcR2-5′ AS interacts with GATA-3 to upregulate chemokine genes necessary for Th2 migration (73).	Flicr negatively regulates FOXP3 leading to decreased Treg function (74). Lnc-Smad-3 regulates TGFβ mediated Treg differentiation by interacting with HDAC1 (75). Lnc-EGFR promotes Treg differentiation through interactions with EGFR (51).	Overexpression of LncRNA-1700040D17Rik was associated with decreased expression of RORγt and IL-17 in Th17 cells (76).