De novo DNA methylation is dispensable for the initiation and propagation of X chromosome inactivation

Takashi Sado, Masaki Okano, En Li, Hiroyuki Sasaki

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Xist (X-inactive specific transcript) plays a crucial role in X-inactivation. This non-coding RNA becomes upregulated on the X chromosome that is to be inactivated upon differentiation. Previous studies have revealed that although maintenance-type DNA methylation is not essential for X-inactivation to occur, it is required for the stable repression of Xist in differentiated cells. However, it is unknown whether differential de novo, methylation at the Xist promoter, which is mediated by Dnmt3a and/or Dnmt3b, is a cause or a consequence of monoallelic expression of Xist. We show that Xist expression is appropriately regulated in the absence of Dnmt3a and Dnmt3b and that a single X chromosome undergoes proper inactivation in mutant females. Our results indicate that a mechanism(s) other than DNA methylation plays a principal role in initiating X-inactivation. We also demonstrate that delayed upregulation of Xist does not induce X-inactivation, consistent with a crucial developmental window for the chromosomal silencing.

Original languageEnglish
Pages (from-to)975-982
Number of pages8
JournalDevelopment
Volume131
Issue number5
DOIs
Publication statusPublished - Mar 2004

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

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