» Articles » PMID: 38551746

Unraveling the Role of Xist in X Chromosome Inactivation: Insights from Rabbit Model and Deletion Analysis of Exons and Repeat A

Overview
Publisher Springer
Specialty Biology
Date 2024 Mar 29
PMID 38551746
Authors
Affiliations
Soon will be listed here.
Abstract

X chromosome inactivation (XCI) is a process that equalizes the expression of X-linked genes between males and females. It relies on Xist, continuously expressed in somatic cells during XCI maintenance. However, how Xist impacts XCI maintenance and its functional motifs remain unclear. In this study, we conducted a comprehensive analysis of Xist, using rabbits as an ideal non-primate model. Homozygous knockout of exon 1, exon 6, and repeat A in female rabbits resulted in embryonic lethality. However, XX females, with intact X chromosome expressing Xist, showed no abnormalities. Interestingly, there were no significant differences between females with homozygous knockout of exons 2-5 and wild-type rabbits, suggesting that exons 2, 3, 4, and 5 are less important for XCI. These findings provide evolutionary insights into Xist function.

References
1.
Tamura K, Nei M, Kumar S . Prospects for inferring very large phylogenies by using the neighbor-joining method. Proc Natl Acad Sci U S A. 2004; 101(30):11030-5. PMC: 491989. DOI: 10.1073/pnas.0404206101. View

2.
Lorenz R, Bernhart S, Honer Zu Siederdissen C, Tafer H, Flamm C, Stadler P . ViennaRNA Package 2.0. Algorithms Mol Biol. 2011; 6:26. PMC: 3319429. DOI: 10.1186/1748-7188-6-26. View

3.
Yang C, Chapman A, Kelsey A, Minks J, Cotton A, Brown C . X-chromosome inactivation: molecular mechanisms from the human perspective. Hum Genet. 2011; 130(2):175-85. DOI: 10.1007/s00439-011-0994-9. View

4.
Lee H, Gopalappa R, Sunwoo H, Choi S, Ramakrishna S, Lee J . En bloc and segmental deletions of human XIST reveal X chromosome inactivation-involving RNA elements. Nucleic Acids Res. 2019; 47(8):3875-3887. PMC: 6486550. DOI: 10.1093/nar/gkz109. View

5.
Chu C, Zhang Q, da Rocha S, Flynn R, Bharadwaj M, Calabrese J . Systematic discovery of Xist RNA binding proteins. Cell. 2015; 161(2):404-16. PMC: 4425988. DOI: 10.1016/j.cell.2015.03.025. View