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• W4378713713 abstract "Abstract X-chromosome inactivation (XCI) epigenetically silences one X chromosome in every cell in female mammals. Although the majority of X-linked genes are silenced, in humans 20% or more are able to escape inactivation and continue to be expressed. Such escape genes are important contributors to sex differences in gene expression, and may impact the phenotypes of X aneuploidies; yet the mechanisms regulating escape from XCI are not understood. We have performed an enrichment analysis of transcription factor binding on the X chromosome, providing new evidence for enriched factors at the transcription start sites of escape genes. The top escape-enriched transcription factors were detected at the RPS4X promoter, a well-described human escape gene previously demonstrated to escape from XCI in a transgenic mouse model. Using a cell line model system that allows for targeted integration and inactivation of transgenes on the mouse X chromosome, we further assessed combinations of RPS4X promoter and genic elements for their ability to drive escape from XCI. We identified a small transgenic construct of only 6 kb capable of robust escape from XCI, establishing that gene-proximal elements are sufficient to permit escape, and highlighting the additive effect of multiple elements that work together in a context-specific fashion." @default.
• W4378713713 created "2023-05-30" @default.
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• W4378713713 date "2022-06-01" @default.
• W4378713713 modified "2023-09-26" @default.
• W4378713713 title "Refining the genomic determinants underlying escape from X-chromosome inactivation" @default.
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• W4378713713 doi "https://doi.org/10.1093/nargab/lqad052" @default.
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• W4378713713 hasPublicationYear "2022" @default.
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