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

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Gene Expression Regulation, Developmental*
  • Genes, X-Linked*
  • Mice
  • RNA, Long Noncoding / metabolism
  • Sequence Analysis, RNA
  • Ubiquitin-Protein Ligases / metabolism*
  • X Chromosome Inactivation

Substances

  • RNA, Long Noncoding
  • XIST non-coding RNA
  • Rlim protein, mouse
  • Ubiquitin-Protein Ligases