Table 1.

The protein partners of CTCF in the 3D genome.

Functional Classification	Partners	Cells	Experimental Evidence	Functional Description	Ref.
Loop extrusion	Cohesion	ES cells, Jurkat cells	Co-IP, Chip	binding to DNA and extruding loops	[10,11,12,13]
	WAPL	-	-	releasing cohesin from DNA templates	[14,15]
	NIPBL	-	-	stimulating the ATPase activity of cohesin	[16]
Transcription	RNA polymerase II	HeLa cells, K562 cells	Co-IP, Chip	regulating transcription and alternative splicing	[17,18]
ES cell development	Oct4	ES cells	Co-IP, Chip	regulating XCI by triggering X chromosome pairing and counting	[19]
	Wdr5	ES cells	Co-IP, Chip	acting as a downstream target of CTCF, and maintaining ES cell pluripotency and somatic reprogramming	[20]
	WIZ	ES cells	Co-IP, Chip	acting as a structural regulator of DNA loops, and maintaining ES cell pluripotency and embryonic development	[21,22,23]
	TAF3	ES cells	Co-IP, Chip	mediating long-range chromatin regulation, supporting ES cells differentiate into endoderm	[24]
Immune cell development	Oct-1	Naive T cells	Co-IP, Chip	regulating naive T-cell differentiation to the Th17 lineage by mediating the contacts of the Th2 locus with the IL-17 locus	[25]
	TCF-1	T cells	Chip	regulating early T-cell development by modulating the TAD boundary formation and long-range chromatin interactions	[26,27]
	Arie	Medullary thymic epithelial cells	Co-IP, Chip	controlling immunological tolerance by promoting superenhancer–promoter loop formation	[28]
	ZNF143	Hematopoietic stem and progenitor cells	Co-IP, Chip	maintaining the integrity of mouse hematopoietic stem and progenitor cells by regulating CTCF-bound promoter–enhancer loops	[29,30,31,32]
	LDB1	MEL cells	Co-IP, Chip	mediating erythroid lineage-specific long-range enhancer interactions	[33]
Muscle cell development	MyoD	Muscle cells	Chip	forming distinct chromatin loops with CTCF, and building the unique 3D genome structure of muscle cells	[34,35,36,37,38]
Multiple developmental processes	YY1	ES cells, B cells, NPC cells	Co-IP, Chip	acting as a structural protein of the 3D genome, and mediating long-range DNA contacts	[39,40,41,42,43,44,45,46,47]
	YB-1	Hela cells,	Co-IP, Chip	inhibiting c-myc transcription, and regulating the 5-HTT polymorphic intron 2 enhancer	[48,49]
	SUZ12	Schwann cells	Co-IP, Chip	suppressing the differentiation inhibitory-pathway in Schwann cells	[50]
Potential roles in development	MAZ	K562, HepG2, HeLa	Co-IP, Chip	acting as a structural proteins of the 3D genome, and stabilizing CTCF binding to DNA	[51]
	BHLHE40	HeLa cells	Co-IP, Chip	regulating CTCF genome-wide distribution and long-range chromatin interactions	[52]
	Kaiso	HeLa cells,	Co-IP, Chip	regulating CTCF insulator activity	[53]
	RFX	Raji cells	Co-IP	regulating HLA-DRB1 and HLA-DQA1 gene transcription	[54,55]
	CIITA	Raji cells	Co-IP	regulating HLA-DRB1 and HLA-DQA1 gene transcription	[54,55]
Chromatin remodeling process	H2A.Z	ES cells	Chip	modulating nucleosome unwrapping and CTCF binding sites	[56]
	CDH8	HeLa cells	GST, Chip	regulating CTCF insulator function	[57]
	BPTF	ES cells	Co-IP, Chip	participating in chromatin remodeling, and regulating Klf4 binding near CTCF sites	[58,59]
	BRG1	WiT49, HeLa	Co-IP, Chip	mediating long-range chromatin interactions	[60,61]
	SIN3A	HeLa cells	GST, Chip	modulating the histone deacetylase activity of CTCF	[62]
Nuclear receptor	VDR	THP-1	Chip	inducing 3D chromatin changes upon activation by 1,25(OH)2D3	[63]
	ER	MCF-7	Chip	inducing 3D chromatin changes upon estrogen activation	[64,65]
Liquid–liquid phase separation	RYBP	ES cells	Co-IP, Chip	mediating long-distance interactions between A compartment by phase separation, and regulating the pluripotency of ES cells	[66]

Abbreviations: Co-IP, co-immunoprecipitation; GST, glutathione-S-transferase pull down assay; Chip, chromatin immunoprecipitation; CHART-seq, RNA target sequencing.