Abstract

In humans, sexual dimorphism is associated with the presence of two X chromosomes in the female, whereas males possess only one X and a small and largely degenerate Y chromosome. How do men cope with having only a single X chromosome given that virtually all other chromosomal monosomies are lethal? Ironically, or even typically many might say, women and more generally female mammals contribute most to the job by shutting down one of their two X chromosomes at random. This phenomenon, called X-inactivation, was originally described some 50 years ago by Mary Lyon and has captivated an increasing number of scientists ever since. The fascination arose in part from the realisation that the inactive X corresponded to a dense heterochromatin mass called the “Barr body” whose number varied with the number of Xs within the nucleus and from the many intellectual questions that this raised: How does the cell count the X chromosomes in the nucleus and inactivate all Xs except one? What kind of molecular mechanisms are able to trigger such a profound, chromosome-wide metamorphosis? When is X-inactivation initiated? How is it transmitted to daughter cells and how is it reset during gametogenesis? This review retraces some of the crucial findings, which have led to our current understanding of a biological process that was initially considered as an exception completely distinct from conventional regulatory systems but is now viewed as a paradigm “par excellence” for epigenetic regulation.

Highlights

  • In humans, sexual dimorphism is associated with the presence of two X chromosomes in the female, whereas males possess only one X and a small and largely degenerate Y chromosome

  • The new and seemingly quirky kinds of gene regulation that could not be explained by Mendelian genetics per se laid the groundwork for the concept of epigenetics—a term derived from the fusion of ‘‘genetics’’, referring to the primary DNA code, and ‘‘epigenesis’’, referring to the differential interpretation of the hereditary material within different cell lineages—as being, at least in part, responsible for the relationship between genes and phenotypes [12]

  • Whilst Barr and Bertram did not realise at the time that they were looking at an inactive X chromosome (Xi)—the critical link between the ‘‘Barr’’ body and a condensed X chromosome was to be made only later by Susumu Ohno [14,15]—their observation, along with that relating to the description of two X-linked loci, Tabby and Mottled, able to confer a mosaic coat colour to heterozygous females [16], and the realisation in 1959 that XO female mice were able both to develop normally and to reproduce [17], were critical to the formulation by Mary Lyon of the Xinactivation theory

Read more

Summary

Introduction

Sexual dimorphism is associated with the presence of two X chromosomes in the female, whereas males possess only one X and a small and largely degenerate Y chromosome. With the possible rider that these studies involve the generation of non-physiological Xist expression levels and the use of Xist as a spliced form, a major finding was that of a critical window of time during which Xist was competent to induce transcriptional repression and after which the chromosome becomes refractory to silencing and the maintenance of gene repression is Xist independent [99].

Results
Conclusion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call