X-chromosome upregulation operates on a gene-by-gene basis at transcriptional and translational levels [ChIP-seq]
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ABSTRACT: Female (XX) mice undergo both X-chromosome inactivation (XCI) and X-chromosome upregulation (XCU) to balance X-linked gene dosage with male (XY) mice and autosomes. XCU has also been reported in XY cells, as well as cells with X-chromosome monosomy (XO). The two X-dosage compensation processes have been shown to occur simultaneously; as one X-chromosome is inactivated, the remaining active X-chromosome becomes upregulated. However, it remains unknown if cells sense and adapt gene dosage at the chromosomal level or on a gene-by-gene basis. Here, we demonstrate that mouse embryonic stem cells can compensate gene dosage by XCU when specific regions or genes are deleted. Compensation occurs at both transcriptional and protein levels and on a gene-by-gene basis. Moreover, we provide evidence for autosomal gene dosage compensation in trans. Overall, our findings demonstrate that mammalian cells can sense heterozygous deletions or inactivation of specific chromosome regions or genes and can compensate in a gene-specific manner at the transcriptional or protein level. These results have important implications for understanding the evolution of gene dosage compensation and its relevance to health, and disease.
ORGANISM(S): Mus musculus
PROVIDER: GSE282785 | GEO | 2025/06/19
REPOSITORIES: GEO
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