Mammalian X-linked gene expression is highly regulated as female cells contain two and male one X chromosome (X). To adjust the X gene dosage between genders, female mouse preimplantation embryos undergo an imprinted form of X chromosome inactivation (iXCI) that requires both Rlim (also known as Rnf12) and the long non-coding RNA Xist. Moreover, it is thought that gene expression from the single active X is upregulated to correct for bi-allelic autosomal (A) gene expression. We have combined mouse genetics with RNA-seq on single mouse embryos to investigate functions of Rlim on the temporal regulation of iXCI and Xist. Our results reveal crucial roles of Rlim for the maintenance of high Xist RNA levels, Xist clouds and X-silencing in female embryos at blastocyst stages, while initial Xist expression appears Rlim-independent. We find further that X/A upregulation is initiated in early male and female preimplantation embryos.
- Ingolf Bach
- Oliver J Rando
- Oliver J Rando
- Jeanne B Lawrence
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All mice were housed in the animal facility of UMMS, and utilized according to NIH guidelines and those established by the UMMS Institute of Animal Care and Usage Committee (IACUC protocol #: A-1940-14).
- Kevin Struhl, Harvard Medical School, United States
- Received: June 26, 2016
- Accepted: September 15, 2016
- Accepted Manuscript published: September 19, 2016 (version 1)
- Accepted Manuscript updated: September 20, 2016 (version 2)
- Accepted Manuscript updated: September 20, 2016 (version 3)
- Accepted Manuscript updated: September 20, 2016 (version 4)
- Version of Record published: October 11, 2016 (version 5)
© 2016, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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