Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Mar;125(1):41-50.
doi: 10.1007/s00412-015-0525-x. Epub 2015 Jul 22.

Cis- and trans-regulation in X inactivation

Joke G van Bemmel  1   2 , Hegias Mira-Bontenbal  2 , Joost Gribnau  3
Affiliations
Review

Cis- and trans-regulation in X inactivation

Joke G van Bemmel et al. Chromosoma. 2016 Mar.

Abstract

Female mammalian cells compensate dosage of X-linked gene expression through the inactivation of one of their two X chromosomes. X chromosome inactivation (XCI) in eutherians is dependent on the non-coding RNA Xist that is up-regulated from the future inactive X chromosome, coating it and recruiting factors involved in silencing and altering its chromatin state. Xist lies within the X-inactivation center (Xic), a region on the X that is required for XCI, and is regulated in cis by elements on the X chromosome and in trans by diffusible factors. In this review, we summarize the latest results in cis- and trans-regulation of the Xic. We discuss how the organization of the Xic in topologically associating domains is important for XCI (cis-regulation) and how proteins in the pluripotent state and upon development or differentiation of embryonic stem cells control proper inactivation of one X chromosome (trans-regulation).

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
The cis-regulatory environment and its spatial separation. The Xic is divided (light gray dashed line) in two topologically associated domains (TADs). Xist and Tsix reside in distinct TADs each harboring their own (putative) regulatory elements: the Xist TAD includes Jpx, Ftx, Xpr, and Rnf12, while the Tsix TAD includes Linx, Chic1, Tsx, and Xite. Genes within each TAD are regulated coordinately during differentiation. Wave symbols on top of genes indicate non-coding genes. Tsx appears to have functions as a coding and non-coding gene
Fig. 2
Fig. 2
Trans-regulation of the Xic in ES cells is affected by different diffusible factors. The autosomally encoded pluripotency factor network directly represses activation on Xist is ES cells, or through activation of the repressor of Xist, Tsix. OCT4, SOX2, NANOG, and PRDM14 also repress the activator of XCI, Rnf12. Activation of XCI involves the dose-dependent break down of REX1 by RNF12. REX1 represses Xist and activates Tsix. Autosomally encoded YY1 activates Xist transcription by competing with REX1 for binding to Xist regulatory elements
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Agrelo R, Souabni A, Novatchkova M, et al. SATB1 defines the developmental context for gene silencing by Xist in lymphoma and embryonic cells. Dev Cell. 2009;16:507–516. doi: 10.1016/j.devcel.2009.03.006. - DOI - PMC - PubMed
    1. Aït Yahya-Graison E, Aubert J, Dauphinot L, et al. Classification of human chromosome 21 gene-expression variations in Down syndrome: impact on disease phenotypes. Am J Hum Genet. 2007;81:475–491. doi: 10.1086/520000. - DOI - PMC - PubMed
    1. Anguera MC, Ma W, Clift D, et al. Tsx produces a long noncoding RNA and has general functions in the germline, stem cells, and brain. PLoS Genet. 2011;7 doi: 10.1371/journal.pgen.1002248. - DOI - PMC - PubMed
    1. Augui S, Filion GJ, Huart S, et al. Sensing X chromosome pairs before X inactivation via a novel X-pairing region of the Xic. Science. 2007;318:1632–1636. doi: 10.1126/science.1149420. - DOI - PubMed
    1. Bacher CP, Guggiari M, Brors B, et al. Transient colocalization of X-inactivation centres accompanies the initiation of X inactivation. Nat Cell Biol. 2006;8:293–299. doi: 10.1038/ncb1365. - DOI - PubMed

Publication types

LinkOut - more resources