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REVIEW

Dosage compensation in mammals: fine-tuning the expression of the X chromosome

¹ CNRS UMR218, Curie Institute, 75248 Paris, Cedex 05, France; ² Department of Pathology and Department of Medicine, University of Washington, Seattle, Washington 98195, USA

Mammalian females have two X chromosomes and males have only one. This has led to the evolution of special mechanisms of dosage compensation. The inactivation of one X chromosome in females equalizes gene expression between the sexes. This process of X-chromosome inactivation (XCI) is a remarkable example of long-range, monoallelic gene silencing and facultative heterochromatin formation, and the questions surrounding it have fascinated biologists for decades. How does the inactivation of more than a thousand genes on one X chromosome take place while the other X chromosome, present in the same nucleus, remains genetically active? What are the underlying mechanisms that trigger the initial differential treatment of the two X chromosomes? How is this differential treatment maintained once it has been established, and how are some genes able to escape the process? Does the mechanism of X inactivation vary between species and even between lineages? In this review, X inactivation is considered in evolutionary terms, and we discuss recent insights into the epigenetic changes and developmental timing of this process. We also review the discovery and possible implications of a second form of dosage compensation in mammals that deals with the unique, potentially haploinsufficient, status of the X chromosome with respect to autosomal gene expression.

[Keywords: X inactivation; dosage compensation; epigenetics; monoallelic regulation; imprinting]

E-MAIL Edith.Heard{at}curie.fr; FAX 33-1-4633-3016.

⁴ E-MAIL cdistech{at}u.washington.edu; FAX (206) 543-3644.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1422906

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