Regulation of X-linked gene expression during early mouse development by Rlim
- University of Massachusetts Medical School, United States
- Massachusetts Institute of Technology, United States
- Broad Institute of MIT and Harvard, United States
Abstract
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.
Data availability
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Transcriptome of mouse preimplantation developmentPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE71442).
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Single-cell RNA-Seq reveals dynamic, random monoallelic gene expression in mammalian cellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE45719).
Article and author information
Author details
Funding
National Institutes of Health (R01CA131158)
- Ingolf Bach
National Institutes of Health (R01HD080224)
- Oliver J Rando
National Institutes of Health (DP1ES025458)
- Oliver J Rando
National Institutes of Health (R01GM053234)
- Jeanne B Lawrence
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Kevin Struhl, Harvard Medical School, United States
Ethics
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).
Version history
- 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)
Copyright
© 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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Regulation of X-linked gene expression during early mouse development by Rlim
eLife 5:e19127.
https://doi.org/10.7554/eLife.19127
Further reading
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- Developmental Biology
Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called ‘polonaise movements’, appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.
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- Developmental Biology
- Physics of Living Systems
Geometric criteria can be used to assess whether cell intercalation is active or passive during the convergent extension of tissue.
