Table 1 Factors involved in X chromosome inactivation

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]