X inactivation counting and choice is a stochastic process: Evidence for involvement of an X-linked activator

IH (Iris) Jonkers, Eveline Rentmeester, Frank Grosveld, Joost Gribnau, Kim Monkhorst

Research output: Contribution to journalArticleAcademicpeer-review

126 Citations (Scopus)

Abstract

Female mammalian cells achieve dosage compensation of X-encoded genes by X chromosome inactivation (XCI). This process is thought to involve X chromosome counting and choice. To explore how this process is initiated, we analyzed XCI in tetraploid XXXX, XXXY, and XXYY embryonic stem cells and found that every X chromosome within a single nucleus has an independent probability to initiate XCI. This finding suggests a stochastic mechanism directing XCI counting and choice. The probability is directly proportional to the X chromosome:ploidy ratio, indicating the presence of an X-encoded activator of XCI, that itself is inactivated by the XCI process. Deletion of a region including Xist, Tsix, and Xite still results in XCI on the remaining wild-type X chromosome in female cells. This result supports a stochastic model in which each X chromosome in a nucleus initiates XCI independently and positions an X-encoded trans-acting XCI-activator outside the deleted region.
Original languageUndefined/Unknown
Pages (from-to)410-421
Number of pages12
JournalCell
Volume132
Issue number3
DOIs
Publication statusPublished - 2008

Research programs

  • EMC MGC-02-13-02
  • EMC MGC-02-82-01

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