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lüll Dosage compensation in mammals: fine-tuning the expression of the X chromosome Heard E; Disteche CMGenes Dev 2006[Jul]; 20 (14): 1848-67Mammalian 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.|*Dosage Compensation, Genetic[MESH]|*X Chromosome[MESH]|Amino Acid Sequence[MESH]|Animals[MESH]|Biological Evolution[MESH]|Epigenesis, Genetic[MESH]|Female[MESH]|Genomic Imprinting[MESH]|Male[MESH]|Mammals/*genetics[MESH]|Molecular Sequence Data[MESH]|Spermatogenesis/genetics[MESH]|X Chromosome Inactivation[MESH] |