Regulation of X-linked gene expression during early mouse development by Rlim
Feng Wang,
JongDae Shin,
Jeremy M Shea,
Jun Yu,
Ana Bošković,
Meg Byron,
Xiaochun Zhu,
Alex K Shalek,
Aviv Regev,
Jeanne B Lawrence,
Eduardo M Torres,
Lihua J Zhu,
Oliver J Rando,
Ingolf Bach
Affiliations
Feng Wang
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
JongDae Shin
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States; Department of Cell Biology, College of Medicine, Konyang University, Daejeon, Korea
Jeremy M Shea
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
Jun Yu
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
Ana Bošković
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
Meg Byron
Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, United States
Xiaochun Zhu
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
Alex K Shalek
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, United States; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United States; Ragon Institute of MGH, MIT and Harvard, Cambridge, United States
Aviv Regev
Broad Institute of MIT and Harvard, Cambridge, United States; Department of Biology, Massachusetts Institute of Technology, Cambridge, United States; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, United States
Jeanne B Lawrence
Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, United States
Eduardo M Torres
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
Lihua J Zhu
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States; Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, United States
Oliver J Rando
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
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.
