High-resolution RNA allelotyping along the inactive X chromosome: evidence of RNA polymerase III in regulating chromatin configuration

Sci Rep. 2017 Apr 3:7:45460. doi: 10.1038/srep45460.

Abstract

We carried out padlock capture, a high-resolution RNA allelotyping method, to study X chromosome inactivation (XCI). We examined the gene reactivation pattern along the inactive X (Xi), after Xist (X-inactive specific transcript), a prototype long non-coding RNA essential for establishing X chromosome inactivation (XCI) in early embryos, is conditionally deleted from Xi in somatic cells (Xi∆Xist). We also monitored the behaviors of X-linked non-coding transcripts before and after XCI. In each mutant cell line, gene reactivation occurs to ~6% genes along Xi∆Xist in a recognizable pattern. Genes with upstream regions enriched for SINEs are prone to be reactivated. SINE is a class of retrotransposon transcribed by RNA polymerase III (Pol III). Intriguingly, a significant fraction of Pol III transcription from non-coding regions is not subjected to Xist-mediated transcriptional silencing. Pol III inhibition affects gene reactivation status along Xi∆Xist, alters chromatin configuration and interferes with the establishment XCI during in vitro differentiation of ES cells. These results suggest that Pol III transcription is involved in chromatin structure re-organization during the onset of XCI and functions as a general mechanism regulating chromatin configuration in mammalian cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Cell Line
  • Chromatin / metabolism*
  • Databases, Genetic
  • Genes, X-Linked
  • Mice
  • Polymorphism, Single Nucleotide
  • RNA Interference
  • RNA Polymerase III / antagonists & inhibitors
  • RNA Polymerase III / genetics
  • RNA Polymerase III / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / metabolism
  • Transcription Factors, TFIII / antagonists & inhibitors
  • Transcription Factors, TFIII / genetics
  • Transcription Factors, TFIII / metabolism
  • X Chromosome / genetics*
  • X Chromosome / metabolism

Substances

  • Chromatin
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Transcription Factors, TFIII
  • XIST non-coding RNA
  • transcription factor TFIIIC
  • RNA Polymerase III