Genomes and Genes
x chromosome inactivation
Summary: A dosage compensation process occurring at an early embryonic stage in mammalian development whereby, at random, one X CHROMOSOME of the pair is repressed in the somatic cells of females.
- Schulz E, Heard E. Role and control of X chromosome dosage in mammalian development. Curr Opin Genet Dev. 2013;23:109-15 pubmed publisher..In this review, we discuss the evolution of dosage compensation and how it is controlled during embryogenesis of mammals. In addition we will summarize evidence on the potential role of X chromosome number during early development. ..
- Engreitz J, Pandya Jones A, McDonel P, Shishkin A, Sirokman K, Surka C, et al. The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science. 2013;341:1237973 pubmed publisher..These findings suggest a model in which Xist coats the X chromosome by searching in three dimensions, modifying chromosome structure, and spreading to newly accessible locations...
- Wutz A. Gene silencing in X-chromosome inactivation: advances in understanding facultative heterochromatin formation. Nat Rev Genet. 2011;12:542-53 pubmed publisher..The emerging picture is complex and suggests that chromosome-wide silencing can be partitioned into several steps, the molecular components of which are starting to be defined. ..
- Good J, Giger T, Dean M, Nachman M. Widespread over-expression of the X chromosome in sterile F?hybrid mice. PLoS Genet. 2010;6:e1001148 pubmed publisher..Overall, these data provide evidence for an underlying regulatory basis to reproductive isolation in house mice and underscore the importance of transcriptional regulation of the X chromosome to the evolution of hybrid male sterility. ..
- Barakat T, Jonkers I, Monkhorst K, Gribnau J. X-changing information on X inactivation. Exp Cell Res. 2010;316:679-87 pubmed publisher..b>X chromosome inactivation (XCI) involves various epigenetic mechanisms, including RNA mediated gene silencing in cis, DNA ..
- Pontier D, Gribnau J. Xist regulation and function explored. Hum Genet. 2011;130:223-36 pubmed publisherb>X chromosome inactivation (XCI) is a process in mammals that ensures equal transcript levels between males and females by genetic inactivation of one of the two X chromosomes in females...
- Marchetto M, Carromeu C, Acab A, Yu D, Yeo G, Mu Y, et al. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell. 2010;143:527-39 pubmed publisher..Our model recapitulates early stages of a human neurodevelopmental disease and represents a promising cellular tool for drug screening, diagnosis and personalized treatment. ..
- Dementyeva E, Shevchenko A, Anopriyenko O, Mazurok N, Elisaphenko E, Nesterova T, et al. Difference between random and imprinted X inactivation in common voles. Chromosoma. 2010;119:541-52 pubmed publisher..The data provide new evidence that imprinted X-inactivation is less complete and/or stable than the random form and DNA methylation contributes less to its maintenance. ..
- Gong L, Ren K, Li Y, Liu X, Zhang W, Yao L, et al. Determination of clonal status of pulmonary sclerosing hemangioma with X-chromosome inactivation mosaicism and polymorphism of phosphoglycerate kinase and androgen receptor genes. Med Oncol. 2011;28:913-8 pubmed publisher..Thus, we concluded that the entire PSH lesion, polygonal and cuboidal cells were neoplastic hyperplasia and originated from a common progenitor cell...
- Grasshoff U, Bonin M, Goehring I, Ekici A, Dufke A, Cremer K, et al. De novo MECP2 duplication in two females with random X-inactivation and moderate mental retardation. Eur J Hum Genet. 2011;19:507-12 pubmed publisher..Furthermore, we describe the phenotype that might be restricted to unspecific mild-to -moderate mental retardation with neurological features in early adulthood. ..
- Grant J, Mahadevaiah S, Khil P, Sangrithi M, Royo H, Duckworth J, et al. Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation. Nature. 2012;487:254-8 pubmed publisher..Our findings permit comparative studies of X-chromosome inactivation in mammals and pose questions about the mechanisms by which X-chromosome inactivation is achieved in eutherians. ..
- Kemkemer C, Hense W, Parsch J. Fine-scale analysis of X chromosome inactivation in the male germ line of Drosophila melanogaster. Mol Biol Evol. 2011;28:1561-3 pubmed publisher..There was no evidence for regions of the X chromosome escaping inactivation, including cytological region 19, which appears to be a hot spot for newly evolved, testis-expressed genes. ..
- van den Berg I, Galjaard R, Laven J, van Doorninck J. XCI in preimplantation mouse and human embryos: first there is remodelling…. Hum Genet. 2011;130:203-15 pubmed publisher..In this review, we describe these differences with respect to initiation of XCI in human and mouse preimplantation embryos, the extra-embryonic tissues and the in vitro model of the epiblast: the embryonic stem cells. ..
- Migeon B. The single active X in human cells: evolutionary tinkering personified. Hum Genet. 2011;130:281-93 pubmed publisher..Further, I suggest that the initial events in the process-those that precede silencing of future inactive X chromosomes-include randomly choosing the future active X, most likely by repressing its XIST locus. ..
- Bruck T, Benvenisty N. Meta-analysis of the heterogeneity of X chromosome inactivation in human pluripotent stem cells. Stem Cell Res. 2011;6:187-93 pubmed publisherIn mammals, X chromosome inactivation (XCI) is a process in which one of the two X chromosomes is silenced, following XIST expression. Mouse female pluripotent stem cells do not express Xist, and harbor two active X chromosomes...
- Simon M, Pinter S, Fang R, Sarma K, Rutenberg Schoenberg M, Bowman S, et al. High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation. Nature. 2013;504:465-469 pubmed publisher..We conclude that Xist spreading takes distinct stage-specific forms. During initial establishment, Xist follows a two-step mechanism, but during maintenance, Xist spreads rapidly to both gene-rich and gene-poor regions. ..
- Kobayashi S, Fujihara Y, Mise N, Kaseda K, Abe K, Ishino F, et al. The X-linked imprinted gene family Fthl17 shows predominantly female expression following the two-cell stage in mouse embryos. Nucleic Acids Res. 2010;38:3672-81 pubmed publisher..This discovery will be important for the study of early sex differentiation, as clearly these differences arise before gonadal differentiation. ..
- Barakat T, Gunhanlar N, Pardo C, Achame E, Ghazvini M, Boers R, et al. RNF12 activates Xist and is essential for X chromosome inactivation. PLoS Genet. 2011;7:e1002001 pubmed publisher..Initiation of random X chromosome inactivation (XCI) is thought to be regulated by X-encoded activators and autosomally encoded suppressors controlling ..
- Senner C, Nesterova T, Norton S, Dewchand H, Godwin J, Mak W, et al. Disruption of a conserved region of Xist exon 1 impairs Xist RNA localisation and X-linked gene silencing during random and imprinted X chromosome inactivation. Development. 2011;138:1541-50 pubmed publisher..Analysis of cells that express Xist(INV) RNA demonstrates reduced association of the mutant RNA to the X chromosome, suggesting that conserved sequences in the inverted region are important for Xist RNA localisation. ..
- Sado T, Sakaguchi T. Species-specific differences in X chromosome inactivation in mammals. Reproduction. 2013;146:R131-9 pubmed publisher..and its subsequent isolation of the mouse homolog, Xist, in the early 1990s, the molecular basis of X chromosome inactivation (X-inactivation) has been more fully elucidated using genetically manipulated mouse embryos and ..
- Ahn J, Lee J. Retinoic acid accelerates downregulation of the Xist repressor, Oct4, and increases the likelihood of Xist activation when Tsix is deficient. BMC Dev Biol. 2010;10:90 pubmed publisher..We propose that the likelihood of Xist expression is determined by a balance of multiple Xist activators and repressors, and that levels of Oct4 and Tsix are crucial toward achieving this balance. ..
- Namekawa S, Payer B, Huynh K, Jaenisch R, Lee J. Two-step imprinted X inactivation: repeat versus genic silencing in the mouse. Mol Cell Biol. 2010;30:3187-205 pubmed publisher..In marsupials and in the early mouse embryo, X chromosome inactivation (XCI) is imprinted to occur selectively on the paternal X chromosome (X(P))...
- Ohhata T, Senner C, Hemberger M, Wutz A. Lineage-specific function of the noncoding Tsix RNA for Xist repression and Xi reactivation in mice. Genes Dev. 2011;25:1702-15 pubmed publisher..This finding shows that reversible XCI is not exclusive to pluripotent cells, and that in some lineages cell differentiation is not accompanied by a stabilization of the Xi. ..
- Pasque V, Gillich A, Garrett N, Gurdon J. Histone variant macroH2A confers resistance to nuclear reprogramming. EMBO J. 2011;30:2373-87 pubmed publisher..Our results uncover the decreased stability of the Xi in EpiSCs, and highlight the importance of combinatorial epigenetic repression involving macroH2A in restricting transcriptional reprogramming by oocytes. ..
- Pinter S, Sadreyev R, Yildirim E, Jeon Y, Ohsumi T, Borowsky M, et al. Spreading of X chromosome inactivation via a hierarchy of defined Polycomb stations. Genome Res. 2012;22:1864-76 pubmed publisherb>X chromosome inactivation (XCI) achieves dosage balance in mammals by repressing one of two X chromosomes in females...
- McGraw S, Oakes C, Martel J, Cirio M, de Zeeuw P, Mak W, et al. Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females. PLoS Genet. 2013;9:e1003873 pubmed publisher..with maternal DNMT1o deficiency provides evidence of additional roles beyond the maintenance of genomic imprints for DNA methylation events in the preimplantation embryo, including a role in imprinted X chromosome inactivation.
- Basu R, Zhang L. X chromosome inactivation: a silence that needs to be broken. Genesis. 2011;49:821-34 pubmed publisher..This phenomenon, called X chromosome inactivation, is a perfect epigenetic event, in which two chromosomes with identical DNA sequences are solely ..
- Morey C, Avner P. Genetics and epigenetics of the X chromosome. Ann N Y Acad Sci. 2010;1214:E18-33 pubmed publisher..Our review analyses how XCI affects the expression of X-linked mutations, describes some of the most recent discoveries on the molecular mechanisms triggering XCI, and explores the therapeutic potentialities of the XCI process per se. ..
- Laisk T, Haller Kikkatalo K, Laanpere M, Jakovlev U, Peters M, Karro H, et al. Androgen receptor epigenetic variations influence early follicular phase gonadotropin levels. Acta Obstet Gynecol Scand. 2010;89:1557-63 pubmed publisher..our results suggest that AR-CAG variations and XCI pattern exert an effect on FSH and LH values, and also have the potential to influence the etiopathogenesis of POF. ..
- Navarro P, Oldfield A, Legoupi J, Festuccia N, Dubois A, Attia M, et al. Molecular coupling of Tsix regulation and pluripotency. Nature. 2010;468:457-60 pubmed publisher..The holistic pattern of Xist/Tsix regulation by pluripotent factors that we have identified suggests a general direct governance of complex epigenetic processes by the machinery dedicated to pluripotency. ..
- Jeon Y, Lee J. YY1 tethers Xist RNA to the inactive X nucleation center. Cell. 2011;146:119-33 pubmed publisher..Specific YY1-to-RNA and YY1-to-DNA contacts are required to load Xist particles onto X. YY1 interacts with Xist RNA through Repeat C. We propose that YY1 acts as adaptor between regulatory RNA and chromatin targets. ..
- Mayo S, Monfort S, Rosello M, Orellana C, Oltra S, Armstrong J, et al. De novo interstitial triplication of MECP2 in a girl with neurodevelopmental disorder and random X chromosome inactivation. Cytogenet Genome Res. 2011;135:93-101 pubmed publisher..that the triplication leads to a severe phenotype due to random X-inactivation, while the preferential X chromosome inactivation in healthy carriers may be caused by a negative selection effect of the duplication on some proximal ..
- Gafni O, Weinberger L, Mansour A, Manor Y, Chomsky E, Ben Yosef D, et al. Derivation of novel human ground state naive pluripotent stem cells. Nature. 2013;504:282-6 pubmed publisher..predominant use of the proximal enhancer element to maintain OCT4 expression, pronounced tendency for X chromosome inactivation in most female human ES cells, increase in DNA methylation and prominent deposition of H3K27me3 and ..
- Soltanzadeh P, Friez M, Dunn D, von Niederhausern A, Gurvich O, Swoboda K, et al. Clinical and genetic characterization of manifesting carriers of DMD mutations. Neuromuscul Disord. 2010;20:499-504 pubmed publisher..Our results demonstrate that improved molecular diagnostic methods facilitate the identification of DMD mutations in manifesting carriers, and confirm the heterogeneity of mutational mechanisms as well as the wide spectrum of phenotypes...
- Gontan C, Achame E, Demmers J, Barakat T, Rentmeester E, van Ijcken W, et al. RNF12 initiates X-chromosome inactivation by targeting REX1 for degradation. Nature. 2012;485:386-90 pubmed publisher..Rex1 and Xist are present only in placental mammals, which points to co-evolution of these two genes and X-chromosome inactivation. ..
- Sadreyev R, Yildirim E, Pinter S, Lee J. Bimodal quantitative relationships between histone modifications for X-linked and autosomal loci. Proc Natl Acad Sci U S A. 2013;110:6949-54 pubmed publisher..Our analysis reveals nontrivial relationships between H3K4me3 and H3K27me3, reveals unique aspects of gene bivalency, and demonstrates that XCI does not conform neatly to autosomal models. ..
- Yang C, McLeod A, Cotton A, de Leeuw C, Laprise S, Banks K, et al. Targeting of >1.5 Mb of human DNA into the mouse X chromosome reveals presence of cis-acting regulators of epigenetic silencing. Genetics. 2012;192:1281-93 pubmed publisherRegulatory sequences can influence the expression of flanking genes over long distances, and X chromosome inactivation is a classic example of cis-acting epigenetic gene regulation...
- Zakharova I, Shevchenko A, Shilov A, Nesterova T, Vandeberg J, Zakian S. Histone H3 trimethylation at lysine 9 marks the inactive metaphase X chromosome in the marsupial Monodelphis domestica. Chromosoma. 2011;120:177-83 pubmed publisherIn somatic cells of female marsupial and eutherian mammals, X chromosome inactivation (XCI) occurs...
- Pullirsch D, HÃ¤rtel R, Kishimoto H, Leeb M, Steiner G, Wutz A. The Trithorax group protein Ash2l and Saf-A are recruited to the inactive X chromosome at the onset of stable X inactivation. Development. 2010;137:935-43 pubmed publisher..This observation highlights a crucial role for spatial organization of chromatin changes in the maintenance of X inactivation. ..
- Shevchenko A, Malakhova A, Elisaphenko E, Mazurok N, Nesterova T, Brockdorff N, et al. Variability of sequence surrounding the Xist gene in rodents suggests taxon-specific regulation of X chromosome inactivation. PLoS ONE. 2011;6:e22771 pubmed publisher..Overall, our data show that not all the functional elements surrounding Xist in mice are well conserved even within rodents, thereby suggesting that the regulation of XCI may be at least partially taxon-specific. ..
- Navarro P, Avner P. An embryonic story: analysis of the gene regulative network controlling Xist expression in mouse embryonic stem cells. Bioessays. 2010;32:581-8 pubmed publisher..In this paper we summarise recent advances in our knowledge of the regulation of Xist and Tsix in embryonic stem (ES) and differentiating ES cells. ..
- Changolkar L, Singh G, Cui K, Berletch J, Zhao K, Disteche C, et al. Genome-wide distribution of macroH2A1 histone variants in mouse liver chromatin. Mol Cell Biol. 2010;30:5473-83 pubmed publisher..Genes that escape X inactivation stand out as domains of macroH2A1 depletion. The rarity of such genes indicates that few genes escape X inactivation in mouse liver, in contrast to what has been observed in human cells. ..
- Murakami K, Araki K, Ohtsuka S, Wakayama T, Niwa H. Choice of random rather than imprinted X inactivation in female embryonic stem cell-derived extra-embryonic cells. Development. 2011;138:197-202 pubmed publisher..Moreover, cloned embryos generated by the transfer of nuclei from the female ES cells showed random Xi in TE, suggesting the complete erasure of all X imprints for imprinted Xi in ICM-derived ES cells...
- Seidel M, Rami B, Item C, Schober E, Zeitlhofer P, Huber W, et al. Concurrent FOXP3- and CTLA4-associated genetic predisposition and skewed X chromosome inactivation in an autoimmune disease-prone family. Eur J Endocrinol. 2012;167:131-4 pubmed publisherCLTA4 is relevant for FOXP3(+)Treg cells, and the link between skewed X chromosome inactivation (XCI) and autoimmunity is recognized...
- Jeon Y, Sarma K, Lee J. New and Xisting regulatory mechanisms of X chromosome inactivation. Curr Opin Genet Dev. 2012;22:62-71 pubmed publisher..This process, termed X chromosome inactivation (XCI), is a quintessential epigenetic phenomenon and involves a complex interplay between noncoding RNAs ..
- Sun S, Fukue Y, Nolen L, Sadreyev R, Lee J. Characterization of Xpr (Xpct) reveals instability but no effects on X-chromosome pairing or Xist expression. Transcription. 2010;1:46-56 pubmed publisher..We conclude that, while Xpr contains unusual properties, it most likely does not serve as a pairing or counting element. Differences in statistical methods and controls may explain some of the discrepancies. ..
- Nora E, Lajoie B, Schulz E, Giorgetti L, Okamoto I, Servant N, et al. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature. 2012;485:381-5 pubmed publisher..In addition to uncovering a new principle of cis-regulatory architecture of mammalian chromosomes, our study sets the stage for the full genetic dissection of the X-inactivation centre...
- Schuring A, Welp A, Gromoll J, Zitzmann M, Sonntag B, Nieschlag E, et al. Role of the CAG repeat polymorphism of the androgen receptor gene in polycystic ovary syndrome (PCOS). Exp Clin Endocrinol Diabetes. 2012;120:73-9 pubmed publisher..We investigated the role of the CAG repeat polymorphism of the androgen receptor in PCOS...
- Chan K, Zhang H, Malureanu L, van Deursen J, Zhang Z. Diverse factors are involved in maintaining X chromosome inactivation. Proc Natl Acad Sci U S A. 2011;108:16699-704 pubmed publisherb>X chromosome inactivation (XCI) is the most dramatic example of epigenetic silencing in eukaryotes. Once established, the inactivated X chromosome (Xi) remains silenced throughout subsequent cell divisions...