D-repeat in the XIST gene is required for X chromosome inactivation

RNA Biol. 2016;13(2):172-6. doi: 10.1080/15476286.2015.1137420.

Abstract

XIST is a long non-coding RNA, which expressed exclusively from the inactive X chromosome. Although it has been revealed that the A-repeat contributes to the X chromosome inactivation (X-inactivation), the role of the longest D-repeat has not yet been investigated. Here, a sgRNA directed CRISPR/Cas9 system which have multiple target sites within repeat D of XIST, were used to generate D-repeat deletion and studied its roles on X-inactivation. The results showed that the deletion of D-repeat caused a significantly decreased expression of XIST, and up regulated expression of X-linked genes, suggesting that the D-repeat may play an important role in the regulation of XIST expression and silencing of the X-linked genes, which could provide a new idea in the molecular mechanisms of X-inactivation.

Keywords: CRISPR/Cas9; D-repeat; XIST; X-inactivation; long non-coding RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CRISPR-Cas Systems
  • Cell Differentiation / genetics*
  • Chromosomes, Human, Y
  • Gene Expression Regulation, Developmental
  • Genes, X-Linked*
  • HEK293 Cells
  • Humans
  • In Situ Hybridization, Fluorescence
  • RNA, Long Noncoding / genetics*
  • Repetitive Sequences, Nucleic Acid
  • X Chromosome Inactivation / genetics*

Substances

  • RNA, Long Noncoding
  • XIST non-coding RNA