X-chromosome inactivation which takes place in early embryogenesis of all higher mammals is largely determined by the Xist gene activity. This gene encodes long untranslated RNA, which provides transcriptional silencing of the genes on chromosome. In the present study, three enhancer and three silencing transcriptional elements were identified in the Xist promoter region. In these regions, location of putative transcription factors was demonstrated, including the ER site, which was discovered in two positions. The effect of estradiol and retinoic acid on the promoter activity was investigated. The estradiol-induced increase of the promoter activity was demonstrated. A model of the estrogen effect on X chromosome inactivation was suggested.
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Biol Sex Differ
January 2025
Department of Laboratory Medicine and Pathology, School of Medicine, University of Washington, Seattle, WA, 98195, USA.
Background: X chromosome inactivation (XCI) is a female-specific process in which one X chromosome is silenced to balance X-linked gene expression between the sexes. XCI is initiated in early development by upregulation of the lncRNA Xist on the future inactive X (Xi). A subset of X-linked genes escape silencing and thus have higher expression in females, suggesting female-specific functions.
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Department of Ecology, Evolution and Marine Biology, University of California Santa Barbara, Santa Barbara, USA.
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October 2024
Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Xist, a pivotal player in X chromosome inactivation (XCI), has long been perceived as a cis-acting long noncoding RNA that binds exclusively to the inactive X chromosome (Xi). However, Xist's ability to diffuse under select circumstances has also been documented, leading us to suspect that Xist RNA may have targets and functions beyond the Xi. Here, using female mouse embryonic stem cells (ES) and mouse embryonic fibroblasts (MEF) as models, we demonstrate that Xist RNA indeed can localize beyond the Xi.
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