Post-translational modifications of PRC2: signals directing its activity

Yang, Yiqi; Li, Gang

doi:10.1186/s13072-020-00369-1

Epigenetics & Chromatin

Table 1 PTMs of PRC2 subunits and their functions

From: Post-translational modifications of PRC2: signals directing its activity

Type of PTM	Subunit	Condition	Modifying enzymes	Sites (human residue)	Function	References
Methylation	EZH2		PRC2	K510, K514 and K515	Facilitates PRC2 access to histone H3K27 substrate, critical for H3K27me3 catalysis	[113, 125]
	SUZ12		PRC2	Unknown	Unknown	[113]
	JARID2		PRC2	K116	Allosteric activation of PRC2	[100]
Phosphorylation	EZH2	IGF-induced	PKB/Akt	S21	Disturbs PRC2 interaction with histone H3, inhibits PRC2 catalytic activity, decreases H3K27me3 level	[126]
			CDK1	T345 (mouse)	Promotes PRC2 interaction with HOTAIR, recruitment, promotes ubiquitin-mediated degradation	[128, 134]
		TNFα	p38α	T372 (mouse)	Enhances PRC2 interaction with YY1, recruitment	[127]
			CDK2	T416	Enhances PRC2 interaction with NIPP1, recruitment	[129, 130]
			AMPK	T311	Disrupts binding to other PRC2 components, inhibits PRC2 catalytic activity	[131]
			JAK3	Y244	Disrupts binding to other PRC2 components, inhibits PRC2 catalytic activity	[132]
			CDK1	T487 (mouse)	Disrupts binding to other PRC2 components, decreases H3K27me3 level, promotes ubiquitin-mediated degradation	[133, 134]
			CDK5	T261	Promotes ubiquitin-mediated degradation	[136]
			JAK2	Y641	Promotes ubiquitin-mediated degradation	[135]
	SUZ12		PLK1	S539, S541 and S546	Disrupts binding to other PRC2 components, promotes ubiquitin-mediated degradation	[137]
	ESC (Drosophila)		CK1/CK2	N-terminus	EED homodimerization and larger PRC2 complex stability	[138]
Acetylation	EZH2		PCAF	K348	Enhances EZH2 stability	[141]
Ubiquitination	EZH2	Neuron differentiation	Smurf2	K421	Promotes EZH2 degradation and subsequent PRC2 disassociation	[144]
		CDK5-mediated phosphorylation at T261	β-TRCP (FBXW1)	Unknown	Promotes EZH2 degradation, inhibits PRC2 catalytic activity	[136]
		JAK2-mediated phosphorylation at Y641	FBXW7	Unknown	Promotes EZH2 degradation, inhibits PRC2 catalytic activity	[135]
	SUZ12	PLK1-mediated phosphorylation at S539, S541 and S546	Unknown	Unknown	Promotes SUZ12 degradation and subsequent PRC2 disassociation	[137]
		DZNep treatment	PRAJA1	Unknown	Promotes EZH2, EED and SUZ12 degradation and subsequent PRC2 disassociation	[145]
SUMOylation	EZH2		Unknown	Unknown	Unknown	[150]
SUMOylation	SUZ12		PIASXβ	K75	Unknown, dispensable for PRC2 localization and catalytical activity	[150]
O-GlcNAcylation	EZH2		OGT	S73, S76, S84, S87 and T313	Enhances stability of isolated EZH2	[154, 155]
O-GlcNAcylation			OGT	S729	Critical for H3K27me2/3 catalysis	[155]

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ISSN: 1756-8935

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