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
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Despite rapid evolution across eutherian mammals, the X-linked MIR-506 family miRNAs are located in a region flanked by two highly conserved protein-coding genes (SLITRK2 and FMR1) on the X chromosome. Intriguingly, these miRNAs are predominantly expressed in the testis, suggesting a potential role in spermatogenesis and male fertility. Here, we report that the X-linked MIR-506 family miRNAs were derived from the MER91C DNA transposons. Selective inactivation of individual miRNAs or clusters caused no discernible defects, but simultaneous ablation of five clusters containing 19 members of the MIR-506 family led to reduced male fertility in mice. Despite normal sperm counts, motility, and morphology, the KO sperm were less competitive than wild-type sperm when subjected to a polyandrous mating scheme. Transcriptomic and bioinformatic analyses revealed that these X-linked MIR-506 family miRNAs, in addition to targeting a set of conserved genes, have more targets that are critical for spermatogenesis and embryonic development during evolution. Our data suggest that the MIR-506 family miRNAs function to enhance sperm competitiveness and reproductive fitness of the male by finetuning gene expression during spermatogenesis.
