Table 1.

Factors involved in X chromosome inactivation

Factors involved in XCI	Function in the context of XCI	References
Proteins
PRC2	The polycomb repressive complex 2 (PRC2) is known to be recruited early on the inactive X (Xi) during differentiation of embryonic stem cells (ESCs) and embryonic development and catalyzes methylation of histone H3 at K27 on chromatin	[40, 80, 81]
PRC1	The activity of polycomb repressive complex 1 (PRC1) on chromatin reinforces gene silencing by ubiquitylation of histone H2A at K119 and chromatin compaction. The order of recruitment of PRC2 and PRC1 to the Xi is still a matter of debate	[82, 83]
Saf-A (HnrnpU)	The Saf-A (HnrnpU) factor directly binds to Xist and mediates its interaction with chromatin through direct interaction with SARS/MARS elements	[21, 23, 44, 56, 58]
SHARP (Spen)	SHARP (Spen) directly binds to Xist and mediates the functional interaction between Xist and the NCoR complex	[21, 23, 44]
CTCF	The CCCTC-binding factor (CTCF) might work as a genomic insulator. In the context of X chromosome inactivation (XCI), it might serve as a barrier to Xist-induced chromatin reorganization	[21, 67]
SATB1	The special AT-rich sequence-binding protein-1 (SATB1) cellular regulator of higher chromatin organization has a role in the initiation of XCI. However, its precise role in XCI is not clear	[59, 84]
YY1	Yin-Yang 1 (YY1) is a bivalent protein with DNA-binding and RNA-binding motifs. It might have a role in tethering Xist to chromatin (spreading in cis) as well as a role in the regulation of Xist	[44, 60, 85]
SmchD1	The protein structural maintenance of chromosome hinge domain 1 (SmchD1) has a role in maintaining a correct pattern of DNA methylation on the Xi during the maintenance phase of XCI	[21, 86]
WTAP	Wilms’ tumor-associated protein (WTAP) is a splicing factor and interactor with Xist. It is involved in regulating RNA methylation. It might have a role in the post-transcriptional modification of Xist	[21, 23, 44]
LBR	The lamin B receptor (LBR) was recently identified as an Xist-binding protein. It is known to localize with the nuclear lamina and to interact with repressive complexes as well as with lamin B	[21, 23]
Rbm15	Rbm15 belongs to the SPEN family of transcriptional repressors and directly binds to Xist RNA	[23]
hnRNPK	Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an RNA-binding protein that interacts with Xist and plays a role in the Xist-mediated recruitment of repressive chromatin marks	[21, 44]
Oct4, Sox2, Rex1, Nanog, PRDM14, Klf4	Pluripotency factors and epigenetic regulators that have been shown to control XCI through the regulation of Xist and Tsix	[2, 74, 87, 88]
Rnf12	The Rnf12 protein seems to regulate the expression of Xist through degradation of Rex1	[75]
Atrx	The protein alpha thalassemia/mental retardation syndrome X-linked (Atrx) is involved in the recruitment of PRC2 on the inactive X chromosome	[21, 89]
ncRNAs
Xist/Tsix	Xist is the master regulator of XCI, and Tsix is its major antagonist. Regulation of the levels of Xist and Tsix regulates the initiation of XCI	[2]
Jpx	The Jpx ncRNA seems to act as an activator of Xist	[2]
Ftx	The Ftx ncRNA seems to be an Xist activator	[2]
Genomic elements
LINEs	The LINEs class of genomic repeats colocalize with inactive genes in the Xi territory and might have a role in the establishment and maintenance of XCI	[43, 90, 91]
SARS/MARS	Facultative scaffold/matrix attachment regions enriched in open chromatin and gene bodies where Xist accumulates	[7, 66]