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Transient Homologous Chromosome Pairing Marks the Onset of X Inactivation
Abstract
Mammalian X inactivation turns off one female X chromosome to enact dosage compensation between XX and XY individuals. X inactivation is known to be regulated in cis by Xite, Tsix , and Xist , but in principle the two Xs must also be regulated in trans to ensure mutually exclusive silencing. Here, we demonstrate that interchromosomal pairing mediates this communication. Pairing occurs transiently at the onset of X inactivation and is specific to the X-inactivation center. Deleting Xite and Tsix perturbs pairing and counting/choice, whereas their autosomal insertion induces de novo X-autosome pairing. Ectopic X-autosome interactions inhibit endogenous X-X pairing and block the initiation of X-chromosome inactivation. Thus, Tsix and Xite function both in cis and in trans. We propose that Tsix and Xite regulate counting and mutually exclusive choice through X-X pairing.
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Cites
Capturing Chromosome Conformation
Dekker, J., Rippe, K., Dekker, M., & Kleckner, N. (2002) · Science · doi:10.1126/science.1067799 · Cited by 3,652
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Kung, J. T. Y., Colognori, D., & Lee, J. T. (2013) · Genetics · doi:10.1534/genetics.112.146704 · Cited by 1,874
Self-citationThe 3D Genome as Moderator of Chromosomal Communication
Dekker, J., & Mirny, L. (2016) · Cell · doi:10.1016/j.cell.2016.02.007 · Cited by 937
Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions
Lanctôt, C., Cheutin, T., Cremer, M., Cavalli, G., & Cremer, T. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2041 · Cited by 781
Nuclear organization of the genome and the potential for gene regulation
Fraser, P., & Bickmore, W. (2007) · Nature · doi:10.1038/nature05916 · Cited by 734
X-Inactivation, Imprinting, and Long Noncoding RNAs in Health and Disease
Lee, J. T., & Bartolomei, M. S. (2013) · Cell · doi:10.1016/j.cell.2013.02.016 · Cited by 676
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Metadata
- Authors
- Xu, N., Tsai, C.-L., & Lee, J. T.
- Venue
- Science
- Published
- 2006-02-24
- Volume
- 311
- Issue
- 5764
- Pages
- 1149-1152
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2054661742
- Cited by
- 380
- References
- 1
- FWCI
- 26.15
- Type
- journal article
- Language
- en
- Open access
- closed
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