RLIM is dispensable for X-chromosome inactivation in the mouse embryonic epiblast
Program in Gene Function and Expression; Department of Cell and Developmental Biology; Program in Molecular Medicine
Cell Biology | Developmental Biology | Genetics and Genomics
In female mice, two forms of X-chromosome inactivation (XCI) ensure the selective silencing of female sex chromosomes during mouse embryogenesis. Beginning at the four-cell stage, imprinted XCI (iXCI) exclusively silences the paternal X chromosome. Later, around implantation, epiblast cells of the inner cell mass that give rise to the embryo reactivate the paternal X chromosome and undergo a random form of XCI (rXCI). Xist, a long non-coding RNA crucial for both forms of XCI, is activated by the ubiquitin ligase RLIM (also known as Rnf12). Although RLIM is required for triggering iXCI in mice, its importance for rXCI has been controversial. Here we show that RLIM levels are downregulated in embryonic cells undergoing rXCI. Using mouse genetics we demonstrate that female cells lacking RLIM from pre-implantation stages onwards show hallmarks of XCI, including Xist clouds and H3K27me3 foci, and have full embryogenic potential. These results provide evidence that RLIM is dispensable for rXCI, indicating that in mice an RLIM-independent mechanism activates Xist in the embryo proper.
DOI of Published Version
Shin J, Wallingford MC, Gallant J, Marcho C, Jiao B, Byron M, Bossenz M, Lawrence JB, Jones SN, Mager J, Bach I. RLIM is dispensable for X-chromosome inactivation in the mouse embryonic epiblast. Nature. 2014 May 25. doi: 10.1038/nature13286. Link to article on publisher's site
Shin, JongDae; Wallingford, Mary C.; Gallant, Judith; Marcho, Chelsea; Jiao, Baowei; Byron, Meg; Bossenz, Michael; Lawrence, Jeanne B.; Jones, Stephen N.; Mager, Jesse; and Bach, Ingolf, "RLIM is dispensable for X-chromosome inactivation in the mouse embryonic epiblast" (2014). Program in Gene Function and Expression Publications and Presentations. 247.