In mammals, transcriptional inactivation of one X chromosome in female compensates for the dosage of X-linked gene expression between the sexes. Additionally, it is believed that the upregulation of active X chromosome in male and female balances the dosage of X-linked gene expression relative to autosomal genes, as proposed by Ohno. However, the existence of X chromosome upregulation (XCU) remains controversial. Here, we have profiled gene-wise dynamics of XCU in pre-gastrulation mouse embryos at single-cell level and found that XCU is dynamically linked with X chromosome inactivation (XCI); however, XCU is not global like XCI. Moreover, we show that upregulated genes are enriched with activating marks and have enhanced burst frequency. Finally, our In-silico model predicts that recruitment probabilities of activating factors and a surge of these factors upon X-inactivation trigger XCU. Altogether, our study provides significant insight into the gene-wise dynamics and mechanistic basis of XCU during early development and extends support for Ohno's hypothesis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189126 | PMC |
| http://dx.doi.org/10.1016/j.isci.2022.104465 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
genomic rearrangements in a 391 French bilateral periventricular nodular heterotopia cohort: prevalence and phenotypic correlations.
J Med Genet
January 2025
Centres de référence Maladies Rares « Neurogénétique » et « Anomalies du développement », Medical Genetics Departement, CHU de Bordeaux, Bordeaux, France.
Background: loss of function manifests across a broad spectrum of phenotypes, ranging from severe prenatal onset to asymptomatic cases. Bilateral periventricular nodular heterotopia (BPNH) consistently occurs in affected individuals. This retrospective study involving French patients with BPNH evaluates the prevalence of gene dosage anomalies and investigates genotype-phenotype correlations in a large cohort of French patients with BPNH.
View Article and Find Full Text PDFIn mammals, X-linked dosage compensation involves two processes: X-chromosome inactivation (XCI) to balance X chromosome dosage between males and females, and hyperactivation of the remaining X chromosome (Xa-hyperactivation) to achieve X-autosome balance in both sexes. Studies of both processes have largely focused on coding genes and have not accounted for transposable elements (TEs) which comprise 50% of the X-chromosome, despite TEs being suspected to have numerous epigenetic functions. This oversight is due in part to the technical challenge of capturing repeat RNAs, bioinformatically aligning them, and determining allelic origin.
View Article and Find Full Text PDFA Case of X-Linked Agammaglobulinemia and COVID-19 in a Japanese Infant.
J Nippon Med Sch
January 2025
Department of Pediatrics, Nippon Medical School.
An infant was diagnosed as having X-linked agammaglobulinemia (XLA) at age 3 months and was receiving immunoglobulin replacement therapy. He developed SARS-CoV-2 infection at age 7 months and was treated with intravenous immunoglobulin, remdesivir, and dexamethasone. His respiratory symptoms improved quickly, and the infection resolved.
View Article and Find Full Text PDFKDM6A facilitates Xist upregulation at the onset of X inactivation.
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.
View Article and Find Full Text PDFA noncanonical role of roX RNAs in autosomal epigenetic repression.
Nat Commun
January 2025
Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Article Synopsis
- roX RNAs are essential for male development in Drosophila, and their absence leads to male lethality during late larval stages.
- They are known for their role in balancing X-linked gene expression but have shown to also target autosomal genes, which had not been extensively studied before.
- The research highlights that roX RNAs function as both activators of X-linked genes and repressors of autosomal genes through their interactions with specific protein complexes, revealing a complex role in gene regulation.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!