When the lyon(Ized chromosome) roars: Ongoing expression from an inactive X chromosome

Laura Carrel, Carolyn J. Brown

Research output: Contribution to journalReview articlepeer-review

63 Scopus citations

Abstract

A tribute to Mary Lyon was held in October 2016. Many remarked about Lyon’s foresight regarding many intricacies of the X-chromosome inactivation process. One such example is that a year after her original 1961 hypothesis she proposed that genes with Y homologues should escape from X inactivation to achieve dosage compensation between males and females. Fifty-five years later we have learned many details about these escapees that we attempt to summarize in this review, with a particular focus on recent findings. We now know that escapees are not rare, particularly on the human X, and that most lack functionally equivalent Y homologues, leading to their increasingly recognized role in sexually dimorphic traits. Newer sequencing technologies have expanded profiling of primary tissues that will better enable connections to sex-biased disorders as well as provide additional insights into the X-inactivation process. Chromosome organization, nuclear location and chromatin environments distinguish escapees from other X-inactivated genes. Nevertheless, several big questions remain, including what dictates their distinct epigenetic environment, the underlying basis of species differences in escapee regulation, how different classes of escapees are distinguished, and the roles that local sequences and chromosome ultrastructure play in escapee regulation. This article is part of the themed issue ‘X-chromosome inactivation: a tribute to Mary Lyon’.

Original languageEnglish (US)
Article number20160355
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume372
Issue number1733
DOIs
StatePublished - Nov 5 2017

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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