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Dosage compensation in mammals involves silencing of one X chromosome in XX females and requires expression, in cis, of Xist RNA. The X to be inactivated is randomly chosen in cells of the inner cell mass (ICM) at the blastocyst stage of development. Embryonic stem (ES) cells derived from the ICM of female mice have two active X chromosomes, one of which is inactivated as the cells differentiate in culture, providing a powerful model system to study the dynamics of X inactivation. Using microarrays to assay expression of X-linked genes in undifferentiated female and male mouse ES cells, we detect global up-regulation of expression (1.4- to 1.6-fold) from the active X chromosomes, relative to autosomes. We show a similar up-regulation in ICM from male blastocysts grown in culture. In male ES cells, up-regulation reaches 2-fold after 2-3 weeks of differentiation, thereby balancing expression between the single X and the diploid autosomes. We show that silencing of X-linked genes in female ES cells occurs on a gene-by-gene basis throughout differentiation, with some genes inactivating early, others late, and some escaping altogether. Surprisingly, by allele-specific analysis in hybrid ES cells, we also identified a subgroup of genes that are silenced in undifferentiated cells. We propose that X-linked genes are silenced in female ES cells by spreading of Xist RNA through the X chromosome territory as the cells differentiate, with silencing times for individual genes dependent on their proximity to the Xist locus.
Pubmed ID: 18076287 RIS Download
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National institute that leads the federal government in conducting and supporting research on aging and the health and well-being of older people. The Institute seeks to understand the nature of aging and the aging process, and diseases and conditions associated with growing older, in order to extend the healthy, active years of life. In 1974, Congress granted authority to form NIA to provide leadership in aging research, training, health information dissemination, and other programs relevant to aging and older people. Subsequent amendments to this legislation designated NIA as the primary Federal agency on Alzheimer's disease research. Mission The Institute's mission is to: * Support and conduct genetic, biological, clinical, behavioral, social, and economic research on aging. * Foster the development of research and clinician scientists in aging. * Provide research resources. * Disseminate information about aging and advances in research to the public, health care professionals, and the scientific community,among a variety of audiences. Programs NIA sponsors research on aging through extramural and intramural programs. The extramural program funds research and training at universities, hospitals, medical centers, and other public and private organizations nationwide. The intramural program conducts basic and clinical research in Baltimore, MD, and on the NIH campus in Bethesda, MD.
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