ArticleGenome biology2021
Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals.
Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 35 citations in OpenAlex.
- Reprogramming the inactive X chromosome: dynamics and insights from the germline.Biochemical Society transactions · 2026Review
- Article
- The role of m6A RNA methylation in the maintenance of X chromosome inactivation and X-to-autosome dosage compensation in early embryonic lineages.Stem cell reports · 2026Article
- Multi-layered dosage compensation of the avian Z chromosome by increased transcriptional burst frequency and elevated translational rates.Nature communications · 2025Article
- X-chromosome upregulation operates on a gene-by-gene basis at RNA and protein levels.Nature communications · 2025Article
- Hbo1 and Msl complexes preserve differential compaction and H3K27me3 marking of active and inactive X chromosomes during mitosis.Nature cell biology · 2025Article
- Cross-species imputation and comparison of single-cell transcriptomic profiles.Genome biology · 2025Article
- Lineage-specific dynamics of loss of X upregulation during inactive-X reactivation.Stem cell reports · 2024Article
- Cross-species imputation and comparison of single-cell transcriptomic profiles.bioRxiv : the preprint server for biology · 2024Article
- The interferon γ pathway enhances pluripotency and X-chromosome reactivation in iPSC reprogramming.Science advances · 2024Article
- Compensation of gene dosage on the mammalian X.Development (Cambridge, England) · 2024Review
- Epigenomic states contribute to coordinated allelic transcriptional bursting in iPSC reprogramming.Life science alliance · 2024Article
- Inferring regulators of cell identity in the human adult pancreas.NAR genomics and bioinformatics · 2023Article
- RNA stability controlled by mNature structural & molecular biology · 2023Article
- The compleX balancing act of controlling X-chromosome dosage and how it impacts mammalian germline development.The Biochemical journal · 2023Article
- Cohesin controls X chromosome structure remodeling and X-reactivation during mouse iPSC-reprogramming.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Controlled X-chromosome dynamics defines meiotic potential of female mouse in vitro germ cells.The EMBO journal · 2022Article
- Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals.Genome biology · 2021Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrecise gene dosage of the X chromosomes is critical for normal development and cellular function. In mice, XX female somatic cells show transcriptional X chromosome upregulation of their single active X chromosome, while the other X chromosome is inactive. Moreover, the inactive X chromosome is reactivated during development in the inner cell mass and in germ cells through X chromosome reactivation, which can be studied in vitro by reprogramming of somatic cells to pluripotency. How chromatin processes and gene regulatory networks evolved to regulate X chromosome dosage in the somatic state and during X chromosome reactivation remains unclear.
resultsUsing genome-wide approaches, allele-specific ATAC-seq and single-cell RNA-seq, in female embryonic fibroblasts and during reprogramming to pluripotency, we show that chromatin accessibility on the upregulated mammalian active X chromosome is increased compared to autosomes. We further show that increased accessibility on the active X chromosome is erased by reprogramming, accompanied by erasure of transcriptional X chromosome upregulation and the loss of increased transcriptional burst frequency. In addition, we characterize gene regulatory networks during reprogramming and X chromosome reactivation, revealing changes in regulatory states. Our data show that ZFP42/REX1, a pluripotency-associated gene that evolved specifically in placental mammals, targets multiple X-linked genes, suggesting an evolutionary link between ZFP42/REX1, X chromosome reactivation, and pluripotency.
conclusionsOur data reveal the existence of intrinsic compensatory mechanisms that involve modulation of chromatin accessibility to counteract X-to-Autosome gene dosage imbalances caused by evolutionary or in vitro X chromosome loss and X chromosome inactivation in mammalian cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.