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Mechanisms of X-inactivation

  1. Sarah M Duthie

Published Online: 19 APR 2001

DOI: 10.1038/npg.els.0001194

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How to Cite

Duthie, S. M. 2001. Mechanisms of X-inactivation. eLS. .

Author Information

  1. Medical Research Council Clinical Sciences Centre, London, UK

Publication History

  1. Published Online: 19 APR 2001
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Figure 1. Model for initiation of random X-inactivation. (a) Unstable Xist transcript from P0 promoter on both alleles. Both X-chromosomes active (Xa). (b) Upon differentiation, a limited amount of blocking factor binds to only one X-chromosome at random – designated Xa. (c) Transcription switches from P0 to initiation of stable, accumulated Xist RNA from P1/P2 on Xi. Xi inactivates. Unstable P0 transcript still detectable from Xa. (d) Unstable P0 Xist transcript silenced on Xa.

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Figure 2. The process of X-inactivation. (a) Xist RNA switched off during passage through the germline. (b) Both X-chromosomes active in early cleavage-stage embryo. Stable, accumulated Xist signal associated with paternal X (Xp). (c) By midstage blastocyst, Xp inactive and associated with stable Xist signal in extraembryonic lineages (trophectoderm), maternal X (Xm) active. Unstable Xist RNA visible as punctate dot from both Xist alleles in cells of the inner cell mass (ICM). Both X-chromosomes active. (d) At day 5.5 of development, embryo implants and cells of embryo proper begin to differentiate. Random X-inactivation initiated – most cells now show unstable Xist transcript from Xa and stable, accumulating transcript from Xi. (e) By day 8.5, Xi associated with stable, accumulated Xist transcript, unstable Xist RNA from Xa switched off. Xi inactive and Xa active throughout adult life.

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Figure 3. Model for spreading of X-inactivation. (a) Active X-chromosome (Xa) showing waystation elements present in gene-rich Giemsa-light (G-light) bands. Waystations are absent or inaccessible in condensed, gene-poor G-dark bands. (b) Xist RNA transcribed from the Xic region spreads bidirectionally via waystation elements along the X. Binding causes local changes in chromatin conformation, resulting in condensation of G-light bands. (c) Xist RNA stably associated with condensed, inactive X-chromosome (Xi).