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Publication : Nuclear positioning and pairing of X-chromosome inactivation centers are not primary determinants during initiation of random X-inactivation.

First Author  Pollex T Year  2019
Journal  Nat Genet Volume  51
Issue  2 Pages  285-295
PubMed ID  30643252 Mgi Jnum  J:291758
Mgi Id  MGI:6446702 Doi  10.1038/s41588-018-0305-7
Citation  Pollex T, et al. (2019) Nuclear positioning and pairing of X-chromosome inactivation centers are not primary determinants during initiation of random X-inactivation. Nat Genet 51(2):285-295
abstractText  During X-chromosome inactivation (XCI), one of the two X-inactivation centers (Xics) upregulates the noncoding RNA Xist to initiate chromosomal silencing in cis. How one Xic is chosen to upregulate Xist remains unclear. Models proposed include localization of one Xic at the nuclear envelope or transient homologous Xic pairing followed by asymmetric transcription factor distribution at Xist's antisense Xite/Tsix locus. Here, we use a TetO/TetR system that can inducibly relocate one or both Xics to the nuclear lamina in differentiating mouse embryonic stem cells. We find that neither nuclear lamina localization nor reduction of Xic homologous pairing influences monoallelic Xist upregulation or choice-making. We also show that transient pairing is associated with biallelic expression, not only at Xist/Tsix but also at other X-linked loci that can escape XCI. Finally, we show that Xic pairing occurs in wavelike patterns, coinciding with genome dynamics and the onset of global regulatory programs during early differentiation.
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