Table 3.

Chromatin phase-separating proteins.

Protein	Species	SIPS/BIPS	Protein binding mode	Method	Phase	ETC	References
H1	Chicken	SIPS	Interaction with DNA and self-association through C-terminus IDR	In vitro	Liquid	Phosphorylation of C-terminus tail reduces interaction.	117
	Human			HeLa cell imaging	Liquid		88
HP1α/a	Human	SIPS	Hinge interaction with DNA, NTE (N-terminal extension) interaction with Hinge	Single-molecule DNA curtain assay	Liquid		19
	Drosophila			Drosophila, high-resolution 4D analysis using lattice light-sheet microscopy	Liquid (?)	The condensate is not entirely liquid and has static compartments.	20
	Human	BIPS	CD interaction with H3K9me3 mark on nucleosome	Cryo-EM			90
	Mouse			Confocal imaging of fibroblast chromocenter	Collapsed globule	The condensate has impermeable boundaries and exhibits concentration buffering, with coil-to-globule transition.	118
	Human			Hi-C		Heterochromatin-like structures can coalesce with constitutive heterochromatin.	91
	Drosophila			Confocal microscopy of transgenic Drosophila polytene		LacI-HP1a fusion protein induced bridging with distant chromosome sites on polytene.	119
	Drosophila	Both		Simulation & Drosophila embryo pericentromeric heterochromatin live-cell imaging	Liquid	Shows both characteristics of BIPS and SIPS. Condensate characteristics may differ with cell cycle and differentiation.	92
PRC1	Mouse	SIPS	LCDR (Low-complexity disordered region) of CBX2	FRAP with nucleosome controls	Liquid		120
	Mouse	BIPS (?) by histone bridging	AT hook of CBX2 interacts with DNA of chromatin	Live-cell single-molecule tracking (SMT, of mESCs)	Liquid	Condensate formation accelerates the target-search process. Eliminating the AT hook affects condensate formation considerably more than CD.	33
	Human		(RING Subunit) E3 Ubiquitin ligase RNF2 ubiquitinates H2AK119	Removal by RNA interference, ChIP			98
PRC2	Human	BIPS (?) by dimerization	The N-terminal C2 domain of SUZ12, one of the PRC2 subunits, interacts with the surface of RBAP48	X-ray crystallography			121
	Human			Cryo-EM		Dimers promote compaction	122
	Human	BIPS (?) by histone bridging	SET domain of EZH2 subunit interacts with the substrate histone’s nucleosome H3 tail.	Cryo-EM			100
	Drosophila		EED interacts with the H3K27me3 histone mark.	Crystallography and pull-down assay			123
	Human	BIPS (?) by multivalent DNA interaction	Various PRC2 subunits such as EZH2 SBD, CXD, (AEBP2), and EED interact with nucleosomal DNA	Cryo-EM			100
			Multivalent interaction with DNA	AFM		DNA is bent by monomers, bridged by dimers.	124