X chromosome ≈ X chromosome
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The asparagus genome sheds light on the origin and evolution of a young Y chromosome Open
Sex chromosomes evolved from autosomes many times across the eukaryote phylogeny. Several models have been proposed to explain this transition, some involving male and female sterility mutations linked in a region of suppressed recombinati…
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Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X Open
Significance Females have increased immune responsiveness than males, and they are more likely to develop autoimmune disorders. The mechanism underlying these observations is unclear, and hypotheses suggest an important role for the X chro…
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The Implication of Early Chromatin Changes in X Chromosome Inactivation Open
During development, the precise relationships between transcription and chromatin modifications often remain unclear. We use the X chromosome inactivation (XCI) paradigm to explore the implication of chromatin changes in gene silencing. Us…
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A general theory of sexual differentiation Open
A general theory of mammalian sexual differentiation is proposed. All biological sex differences are the result of the inequality in effects of the sex chromosomes, which are the only factors that differ in XX vs. XY zygotes. This inequali…
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XX sex chromosome complement promotes atherosclerosis in mice Open
Men and women differ in circulating lipids and coronary artery disease (CAD). While sex hormones such as estrogens decrease CAD risk, hormone replacement therapy increases risk. Biological sex is determined by sex hormones and chromosomes,…
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PCGF3/5–PRC1 initiates Polycomb recruitment in X chromosome inactivation Open
Polycomb steps to inactivate X XX females silence one of their X chromosomes. This involves a process whereby a noncoding RNA known as Xist coats one of the X chromosomes and recruits chromatin silencing factors. The Polycomb complexes PRC…
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Deletion of <i>DXZ4</i> on the human inactive X chromosome alters higher-order genome architecture Open
Significance In human females, one of the two X chromosomes is inactive (Xi) and adopts an unusual 3D conformation. The Xi chromosome contains superloops, large chromatin loops that are often anchored at the macrosatellite repeat DXZ4 , an…
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X-Chromosome Inactivation: A Crossroads Between Chromosome Architecture and Gene Regulation Open
In somatic nuclei of female therian mammals, the two X chromosomes display very different chromatin states: One X is typically euchromatic and transcriptionally active, and the other is mostly silent and forms a cytologically detectable he…
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Xist RNA in action: Past, present, and future Open
In mammals, dosage compensation of sex chromosomal genes between females (XX) and males (XY) is achieved through X-chromosome inactivation (XCI). The X-linked X-inactive-specific transcript (Xist) long noncoding RNA is indispensable for XC…
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SHAPE reveals transcript-wide interactions, complex structural domains, and protein interactions across the <i>Xist</i> lncRNA in living cells Open
Significance Long noncoding RNAs (lncRNAs) are important regulators of gene expression, but their structural features are largely unknown. We used structure-selective chemical probing to examine the structure of the Xist lncRNA in living c…
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A protein assembly mediates Xist localization and gene silencing Open
Nuclear compartments have diverse roles in regulating gene expression, yet the molecular forces and components that drive compartment formation remain largely unclear1. The long non-coding RNA Xist establishes an intra-chromosomal compartm…
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Sex-chromosome dosage effects on gene expression in humans Open
Significance Sex-chromosome dosage (SCD) effects on human gene expression are central to the biology of sex differences and sex-chromosome aneuploidy syndromes but are challenging to study given the cosegregation of SCD and gonadal status.…
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The X-linked histone demethylase Kdm6a in CD4+ T lymphocytes modulates autoimmunity Open
Multiple sclerosis (MS) is a putative T cell-mediated autoimmune disease. As with many autoimmune diseases, females are more susceptible than males. Sexual dimorphisms may be due to differences in sex hormones, sex chromosomes, or both. Re…
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Mapping the mouse Allelome reveals tissue-specific regulation of allelic expression Open
To determine the dynamics of allelic-specific expression during mouse development, we analyzed RNA-seq data from 23 F1 tissues from different developmental stages, including 19 female tissues allowing X chromosome inactivation (XCI) escape…
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Sex differences in the late first trimester human placenta transcriptome Open
This study is the first characterization of the late first trimester placenta transcriptome, highlighting similarities and differences among the sexes in ongoing human pregnancies resulting in live births. Sexual dimorphism may contribute …
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Altered X-chromosome inactivation in T cells may promote sex-biased autoimmune diseases Open
Systemic lupus erythematosus (SLE) is an autoimmune disorder that predominantly affects women and is driven by autoreactive T cell-mediated inflammation. It is known that individuals with multiple X-chromosomes are at increased risk for de…
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Identification of the master sex determining gene in Northern pike (Esox lucius) reveals restricted sex chromosome differentiation Open
Teleost fishes, thanks to their rapid evolution of sex determination mechanisms, provide remarkable opportunities to study the formation of sex chromosomes and the mechanisms driving the birth of new master sex determining (MSD) genes. How…
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X Inactivation and Escape: Epigenetic and Structural Features Open
X inactivation represents a complex multi-layer epigenetic mechanism that profoundly modifies chromatin composition and structure of one X chromosome in females. The heterochromatic inactive X chromosome adopts a unique 3D bipartite struct…
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome Open
To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events…
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Progress toward understanding chromosome silencing by Xist RNA Open
The X inactive-specific transcript ( Xist ) gene is the master regulator of X chromosome inactivation in mammals. Xist produces a long noncoding (lnc)RNA that accumulates over the entire length of the chromosome from which it is transcribe…
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The sex with the reduced sex chromosome dies earlier: a comparison across the tree of life Open
Many taxa show substantial differences in lifespan between the sexes. However, these differences are not always in the same direction. In mammals, females tend to live longer than males, while in birds, males tend to live longer than femal…
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Widespread DNA hypomethylation and differential gene expression in Turner syndrome Open
Adults with 45,X monosomy (Turner syndrome) reflect a surviving minority since more than 99% of fetuses with 45,X monosomy die in utero. In adulthood 45,X monosomy is associated with increased morbidity and mortality, although strikingly h…
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Sex Determination by Two Y-Linked Genes in Garden Asparagus Open
The origin and early evolution of sex chromosomes have been hypothesized to involve the linkage of factors with antagonistic effects on male and female function. Garden asparagus (Asparagus officinalis) is an ideal species to investigate t…
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Evolution of Sex Chromosome Dosage Compensation in Animals: A Beautiful Theory, Undermined by Facts and Bedeviled by Details Open
Many animals with genetic sex determination harbor heteromorphic sex chromosomes, where the heterogametic sex has half the gene dose of the homogametic sex. This imbalance, if reflected in the abundance of transcripts or proteins, has the …
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Genomic imprinting of <i>Xist</i> by maternal H3K27me3 Open
Maternal imprinting at the Xist gene is essential to achieve paternal allele-specific imprinted X-chromosome inactivation (XCI) in female mammals. However, the mechanism underlying Xist imprinting is unclear. Here we show that the Xist loc…
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Single-Cell RNA-Seq Reveals Cellular Heterogeneity of Pluripotency Transition and X Chromosome Dynamics during Early Mouse Development Open
Following implantation, the epiblast (EPI) cells transit from the naive to primed pluripotency, accompanied by dynamic changes in X chromosome activity in females. To investigate the molecular attributes of this process, we performed singl…
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The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory Open
The nuclear matrix protein Cip1-interacting zinc finger protein 1 (CIZ1) promotes DNA replication in association with cyclins and has been linked to adult and pediatric cancers. Here we show that CIZ1 is highly enriched on the inactive X c…
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Systematic allelic analysis defines the interplay of key pathways in X chromosome inactivation Open
Xist RNA, the master regulator of X chromosome inactivation, acts in cis to induce chromosome-wide silencing. Whilst recent studies have defined candidate silencing factors, their relative contribution to repressing different genes, and th…
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Repeat E anchors Xist RNA to the inactive X chromosomal compartment through CDKN1A-interacting protein (CIZ1) Open
Significance The long noncoding Xist RNA coats and silences one X chromosome in female cells. How Xist localizes in cis to the inactive X compartment is not clear. Here, we reveal a required interaction between CIZ1 protein and Xist Repeat…
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Human genes escaping X-inactivation revealed by single cell expression data Open
BACKGROUND: In mammals, sex chromosomes pose an inherent imbalance of gene expression between sexes. In each female somatic cell, random inactivation of one of the X-chromosomes restores this balance. While most genes from the inactivated …