ArticleNature structural & molecular biology2022
Xist spatially amplifies SHARP/SPEN recruitment to balance chromosome-wide silencing and specificity to the X chromosome.
Article in Nature structural & molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 108 citations in OpenAlex.
- BDNF-DT and BDNF-AS-DT: novel genes in the BDNF locus.Molecular psychiatry · 2026Article
- A continuum-based reaction-diffusion model for spread of gene silencing in chromosomal inactivation.RNA (New York, N.Y.) · 2026Article
- From inactivation to intervention: X chromosome silencing in disease pathogenesis and emerging therapeutic strategies.Genes & diseases · 2026Review
- Peripheral and Central miRNA Signatures in Alzheimer's Disease: Tissue-Specific Variability, Sex-Associated Differences, and Implications for Blood-Based Biomarkers.International journal of molecular sciences · 2026Review
- Correlated protein-RNA associations and a requirement for HNRNPU in the long-range recruitment of Polycomb Repressive Complexes by the lncRNAs Airn and Kcnq1ot1.PLoS genetics · 2026Article
- Using combined RNA/DNA short read sequencing to investigate allele-specific expression from the inactive X chromosome in human cells.bioRxiv : the preprint server for biology · 2026Article
- SETDB1 and HUSH modulate Xist RNA levels during establishment of X chromosome inactivation.Nature communications · 2026Article
- Sex and tissue resolved co-expression networks reveal a female placental-brain axis protective against prenatal PCB exposure.Genome biology · 2026Article
- Comprehensive CRISPR/Cas9-based mutagenesis identifies single-amino acid substitutions that abrogate SPEN function in X inactivation.Nature communications · 2026Article
- Reprogramming the inactive X chromosome: dynamics and insights from the germline.Biochemical Society transactions · 2026Review
- The impact of X chromosome inactivation on human health.Frontiers in genetics · 2026Review
- Escape from X inactivation is directly modulated by Xist noncoding RNA.Nature cell biology · 2026Article
- Xist in X chromosome inactivation: mechanisms and disease relevance.Cell communication and signaling : CCS · 2025Review
- Reporter CRISPR screens decipher cis-regulatory and trans-regulatory principles at the Xist locus.Nature structural & molecular biology · 2025Article
- Convergent evolution of H4K16ac-mediated dosage compensation in the ZW species Artemia franciscana.PLoS genetics · 2025Article
- Article
- Illuminating biomolecular assemblies in gene regulation.Biophysical reviews · 2025Review
- Xist condensates: perspectives for therapeutic intervention.Genome biology · 2025Review
- X chromosome inactivation in mammals: general principles and species-specific considerations.EMBO reports · 2025Review
- Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Although thousands of long non-coding RNAs (lncRNAs) are encoded in mammalian genomes, their mechanisms of action are poorly understood, in part because they are often expressed at lower levels than their proposed targets. One such lncRNA is Xist, which mediates chromosome-wide gene silencing on one of the two X chromosomes (X) to achieve gene expression balance between males and females. How a limited number of Xist molecules can mediate robust silencing of a much larger number of target genes while maintaining specificity exclusively to genes on the X within each cell is not well understood. Here, we show that Xist drives non-stoichiometric recruitment of the essential silencing protein SHARP (also known as SPEN) to amplify its abundance across the inactive X, including at regions not directly occupied by Xist. This amplification is achieved through concentration-dependent homotypic assemblies of SHARP on the X and is required for chromosome-wide silencing. Expression of Xist at higher levels leads to increased localization at autosomal regions, demonstrating that low levels of Xist are critical for ensuring its specificity to the X. We show that Xist (through SHARP) acts to suppress production of its own RNA which may act to constrain overall RNA levels and restrict its ability to spread beyond the X. Together, our results demonstrate a spatial amplification mechanism that allows Xist to achieve two essential but countervailing regulatory objectives: chromosome-wide gene silencing and specificity to the X. This suggests a more general mechanism by which other low-abundance lncRNAs could balance specificity to, and robust control of, their regulatory targets.
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Registered trials
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 OpenQuestion graph.