X-chromosome upregulation is driven by increased burst frequency

Nat Struct Mol Biol. 2019 Oct;26(10):963-969. doi: 10.1038/s41594-019-0306-y. Epub 2019 Oct 3.

Abstract

Ohno's hypothesis postulates that upregulation of X-linked genes rectifies their dosage imbalance relative to autosomal genes, which are present in two active copies per cell. Here we have dissected X-chromosome upregulation into the kinetics of transcription, inferred from allele-specific single-cell RNA sequencing data from somatic and embryonic mouse cells. We confirmed increased X-chromosome expression levels in female and male cells and found that the X chromosome achieved upregulation by elevated burst frequencies. By monitoring transcriptional kinetics in differentiating female mouse embryonic stem cells, we found that increased burst frequency was established on the active X chromosome when X inactivation took place on the other allele. Thus, our study provides mechanistic insights into X-chromosome upregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Cells, Cultured
  • Female
  • Gene Expression Regulation, Developmental
  • Genes, X-Linked
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Transcriptional Activation*
  • Up-Regulation*
  • X Chromosome / genetics*
  • X Chromosome Inactivation