Dosage compensation in mammals: fine-tuning the expression of the X chromosome.
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.
Heard
Edith
E
CNRS UMR218, Curie Institute, Paris, France. Edith.Heard@curie.fr
Disteche
Christine M
CM
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D004303:Dosage Compensation, Genetic; D044127:Epigenesis, Genetic; D005260:Female; D018392:Genomic Imprinting; D008297:Male; D008322:Mammals / Q000235:genetics*; D008969:Molecular Sequence Data; D013091:Spermatogenesis / Q000235:genetics; D014960:X Chromosome; D049951:X Chromosome Inactivation