Xist localization and function: new insights from multiple levels
Open accessAbstract
In female mammals, one of the two X chromosomes in each cell is transcriptionally silenced in order to achieve dosage compensation between the genders in a process called X chromosome inactivation. The master regulator of this process is the long non-coding RNA Xist. During X-inactivation, Xist accumulates in cis on the future inactive X chromosome, triggering a cascade of events that provoke the stable silencing of the entire chromosome, with relatively few genes remaining active. How Xist spreads, what are its binding sites, how it recruits silencing factors and how it induces a specific topological and nuclear organization of the chromatin all remain largely unanswered questions. Recent studies have improved our understanding of Xist localization and the proteins with which it interacts, allowing a reappraisal of ideas about Xist function. We discuss recent advances in our knowledge of Xist-mediated silencing, focusing on Xist spreading, the nuclear organization of the inactive X chromosome, recruitment of the polycomb complex and the role of the nuclear matrix in the process of X chromosome inactivation.
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X inactivation escape, in addition to epigenetic effects on genes on all chromosomes, results in sex/gender differences in the rates of many medical conditions.
“This process, in addition to epigenetic effects on genes on all chromosomes (50, 51), results in sex/gender differences in the rates of many medical conditions.”
From Where Sex Meets Gender: How Sex and Gender Come Together to Cause Sex Differences in Mental Illness (2022) · cites this paper as [50]
The Abstract (page not provided) says that X inactivation silences one X chromosome while relatively few genes remain active, supporting the escape aspect. The cited paper does not link escape to differences in medical-condition rates or describe epigenetic effects on genes on all chromosomes. (LLM, conf=0.83)
Experimental — accuracy not yet measuredBecause females have two X chromosomes, one in each body cell is automatically and randomly inactivated so that males and females end up with an approximately equal total of gene products.
“Because females have two X chromosomes, one in each body cell is automatically and randomly inactivated so that males and females end up with an approximately equal total of gene products (50).”
From Where Sex Meets Gender: How Sex and Gender Come Together to Cause Sex Differences in Mental Illness (2022) · cites this paper as [50]
The Introduction says that silencing one of the two X chromosomes in female cells provides dosage compensation between XX and XY individuals. It also distinguishes random inactivation in mouse inner-cell-mass cells from earlier embryonic inactivation that preferentially affects the paternal X, so it does not support describing X inactivation as uniformly random in every body cell. (LLM, conf=0.87)
Experimental — accuracy not yet measured
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Memili, E., Hong, Y., Kim, D.-H., et al. (2001) · Gene · doi:10.1016/s0378-1119(01)00353-5 · Cited by 33 · see citing works
Satb1 and Satb2 Are Dispensable for X Chromosome Inactivation in Mice
Nechanitzky, R., Dávila, A., Savarese, F., Fietze, S., & Grosschedl, R. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.09.018 · Cited by 26 · see citing works
Long Noncoding RNAs Xist in Three Dimensions
Dimond, A., & Fraser, P. (2013) · Science · doi:10.1126/science.1243257 · Cited by 19 · see citing works
Revisiting the function of nuclear scaffold/matrix binding proteins in X chromosome inactivation
Hasegawa, Y., & Nakagawa, S. (2011) · RNA Biology · doi:10.4161/rna.8.5.16367 · Cited by 10 · see citing works
X-Inactivation: Xist RNA Uses Chromosome Contacts to Coat the X
Leung, K., & Panning, B. (2014) · Current Biology · doi:10.1016/j.cub.2013.11.052 · Cited by 8 · see citing works
Building up the inactive X chromosome1
Matarazzo, M. R., Cerase, A., & D’Esposito, M. (2007) · Biology of the Cell · doi:10.1042/bc20070073 · Cited by 6 · see citing works
Self-citation
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From “Cellular” RNA to “Smart” RNA: Multiple Roles of RNA in Genome Stability and Beyond
Michelini, F., Jalihal, A. P., Francia, S., Meers, C., Neeb, Z. T., Rossiello, F., Gioia, U., Aguado, J., Jones-Weinert, C., Luke, B., et al. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00487 · Cited by 85 · see citing works
Where Sex Meets Gender: How Sex and Gender Come Together to Cause Sex Differences in Mental Illness
Christiansen, D. M., McCarthy, M. M., & Seeman, M. V. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.856436 · Cited by 65 · see citing works
“This process, in addition to epigenetic effects on genes on all chromosomes (50, 51), results in sex/gender differences in the rates of many medical conditions.”
Background
- Authors
- Cerase, A., Pintacuda, G., Tattermusch, A., & Avner, P.
- Affiliations
- European Molecular Biology Laboratory (IT)
- University of Oxford (GB)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Cerase, Andrea
- Avner, Philip
- Venue
- Genome biology
- Published
- 2015-08-15
- Volume
- 16
- Issue
- 1
- Pages
- 166-166
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC4539689
- OpenAlex
- W2137720632
- Cited by
- 189
- References
- 92
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 9 · 2023: 13 · 2022: 18 · 2021: 16 · 2020: 19 · 2019: 29 · 2018: 22 · 2017: 28 · 2016: 13 · 2015: 1 · 2013: 1
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Genome biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Funders
- EMBL (50800)
- Medical Research Council (1036324)
- Wellcome Trust (ID0ETXAG1525)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- XIST, X chromosome inactivation, dosage compensation, long non-coding RNA, inactive X chromosome, nuclear organization, Polycomb complexes, nuclear matrix
- MeSH terms
- Animals, Cell Nucleus, Female, Gene Silencing, X Chromosome Inactivation, Mice, RNA, Long Noncoding, Polycomb-Group Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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