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Elife. 2016 Sep 19;5. pii: e19127. doi: 10.7554/eLife.19127.

Regulation of X-linked gene expression during early mouse development by Rlim.

Author information

1
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States.
2
Department of Cell Biology, College of Medicine, Konyang University, Daejeon, Korea.
3
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States.
4
Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, United States.
5
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, United States.
6
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, United States.
7
Broad Institute of MIT and Harvard, Cambridge, United States.
8
Ragon Institute of MGH, MIT and Harvard, Cambridge, United States.
9
Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.
10
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, United States.
11
Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, 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.

KEYWORDS:

Rlim/Rnf12; X chromosome inactivation; X upregulation; Xist; developmental biology; mouse; mouse preimplantation development; single embryo RNA-seq; stem cells

PMID:
27642011
PMCID:
PMC5059138
DOI:
10.7554/eLife.19127
[Indexed for MEDLINE]
Free PMC Article

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