scholarly journals Loss of p53 Causes Stochastic Aberrant X-Chromosome Inactivation and Female-Specific Neural Tube Defects

Cell Reports ◽  
2019 ◽  
Vol 27 (2) ◽  
pp. 442-454.e5 ◽  
Author(s):  
Alex R.D. Delbridge ◽  
Andrew J. Kueh ◽  
Francine Ke ◽  
Natasha M. Zamudio ◽  
Farrah El-Saafin ◽  
...  
Keyword(s):  
X Chromosome ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Female Specific

scholarly journals Escape from X Chromosome Inactivation and the Female Predominance in Autoimmune Diseases

2021 ◽  
Vol 22 (3) ◽  
pp. 1114
Author(s):  
Ali Youness ◽  
Charles-Henry Miquel ◽  
Jean-Charles Guéry
Keyword(s):  
Autoimmune Diseases ◽  
X Chromosome ◽  
Gene Dosage ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
X Chromosomes ◽  
Female Sex Hormones ◽  
Inactive X Chromosome ◽  
Immune Related Genes ◽  
Female Specific

Women represent 80% of people affected by autoimmune diseases. Although, many studies have demonstrated a role for sex hormone receptor signaling, particularly estrogens, in the direct regulation of innate and adaptive components of the immune system, recent data suggest that female sex hormones are not the only cause of the female predisposition to autoimmunity. Besides sex steroid hormones, growing evidence points towards the role of X-linked genetic factors. In female mammals, one of the two X chromosomes is randomly inactivated during embryonic development, resulting in a cellular mosaicism, where about one-half of the cells in a given tissue express either the maternal X chromosome or the paternal one. X chromosome inactivation (XCI) is however not complete and 15 to 23% of genes from the inactive X chromosome (Xi) escape XCI, thereby contributing to the emergence of a female-specific heterogeneous population of cells with bi-allelic expression of some X-linked genes. Although the direct contribution of this genetic mechanism in the female susceptibility to autoimmunity still remains to be established, the cellular mosaicism resulting from XCI escape is likely to create a unique functional plasticity within female immune cells. Here, we review recent findings identifying key immune related genes that escape XCI and the relationship between gene dosage imbalance and functional responsiveness in female cells.

scholarly journals Xmas ESC: A new female embryonic stem cell system that reveals the BAF complex as a key regulator of the establishment of X chromosome inactivation

2019 ◽  
Author(s):  
Andrew Keniry ◽  
Natasha Jansz ◽  
Linden J. Gearing ◽  
Iromi Wanigasuriya ◽  
Joseph Chen ◽  
...  
Keyword(s):  
X Chromosome ◽  
Embryonic Stem ◽  
X Chromosome Inactivation ◽  
Cell System ◽  
X Inactivation ◽  
Chromosome Inactivation ◽  
Baf Complex ◽  
Specific Process ◽  
Female Specific

SummaryAlthough female pluripotency significantly differs to male, complications with in vitro culture of female embryonic stem cells (ESC) have severely limited the use and study of these cells. We report a replenishable female ESC system, Xmas, that has enabled us to optimise a protocol for preserving the XX karyotype. Our protocol also improves male ESC fitness. We utilised our Xmas ESC system to screen for regulators of the female-specific process of X chromosome inactivation, revealing chromatin remodellers Smarcc1 and Smarca4 as key regulators of establishment of X inactivation. The remodellers create a nucleosome depleted region at gene promotors on the inactive X during exit from pluripotency, without which gene silencing fails. Our female ESC system provides a tractable model for XX ESC culture that will expedite study of female pluripotency and has enabled us to discover new features of the female-specific process of X inactivation.

scholarly journals X-chromosome inactivation and its implications for human disease

2017 ◽  
Author(s):  
Joost Gribnau ◽  
Tahsin Stefan Barakat
Keyword(s):  
X Chromosome ◽  
Human Disease ◽  
Direct Consequence ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Parental Origin ◽  
X Chromosomes ◽  
Clinical Consequences ◽  
Female Specific ◽  
Important Disease

ABSTRACTIn humans and other mammals, female cells carry two X-chromosomes, whereas male cells carry a single X and Y-chromosome. To achieve an equal expression level of X-linked genes in both sexes, a dosage compensation mechanism evolved, which results in transcriptional silencing of one X-chromosome in females. X chromosome inactivation (XCI) is random with respect to the parental origin of the X, occurs early during embryonic development, and is then stably maintained through a near infinite number of cell divisions. As a result of this, every female individual consists of a mosaic of two different cell populations, in which either the maternally or paternally derived X-chromosome is inactivated. As the X-chromosome harbors more than a thousand genes, of which many are implicated in human disease when mutated, this mosaicism has important disease implications. Whereas X-linked disorders are usually more severe in hemizygous males harboring a single X-chromosome, a more variable phenotype is observed in females. This variability is a direct consequence of the XCI-mosaicism, and is affected by the randomness of the XCI process. Here we review the latest insights into the regulation of this important female specific process, and discuss mechanisms that influence mosaicism in females, with a focus on the clinical consequences related to X-linked diseases in females.

X-linked CNV and skewed X-chromosome inactivation

2020 ◽  
pp. 19-21
Author(s):  
Е.А. Фонова ◽  
Е.Н. Толмачева ◽  
А.А. Кашеварова ◽  
М.Е. Лопаткина ◽  
К.А. Павлова ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Intellectual Disability ◽  
X Chromosome ◽  
Copy Number ◽  
Copy Number Variations ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Chromosome X ◽  
Skewed X Chromosome Inactivation

Смещение инактивации Х-хромосомы может быть следствием и маркером нарушения клеточной пролиферации при вариациях числа копий ДНК на Х-хромосоме. Х-сцепленные CNV выявляются как у женщин с невынашиванием беременности и смещением инактивации Х-хромосомы (с частотой 33,3%), так и у пациентов с умственной отсталостью и смещением инактивацией у их матерей (с частотой 40%). A skewed X-chromosome inactivation can be a consequence and a marker of impaired cell proliferation in the presence of copy number variations (CNV) on the X chromosome. X-linked CNVs are detected in women with miscarriages and a skewed X-chromosome inactivation (with a frequency of 33.3%), as well as in patients with intellectual disability and skewed X-chromosome inactivation in their mothers (with a frequency of 40%).

scholarly journals X-Linked Emery–Dreifuss Muscular Dystrophy: Study Of X-Chromosome Inactivation and Its Relation with Clinical Phenotypes in Female Carriers

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 919 ◽  
Author(s):  
Viggiano ◽  
Madej-Pilarczyk ◽  
Carboni ◽  
Picillo ◽  
Ergoli ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
X Chromosome ◽  
Clinical Symptoms ◽  
Fibrous Tissue ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Cardiac Conduction ◽  
Asymptomatic Carriers ◽  
Cardiac Symptoms ◽  
Female Carriers

X-linked Emery–Dreifuss muscular dystrophy (EDMD1) affects approximately 1:100,000 male births. Female carriers are usually asymptomatic but, in some cases, they may present clinical symptoms after age 50 at cardiac level, especially in the form of conduction tissue anomalies. The aim of this study was to evaluate the relation between heart involvement in symptomatic EDMD1 carriers and the X-chromosome inactivation (XCI) pattern. The XCI pattern was determined on the lymphocytes of 30 symptomatic and asymptomatic EDMD1 female carriers—25 familial and 5 sporadic cases—seeking genetic advice using the androgen receptor (AR) methylation-based assay. Carriers were subdivided according to whether they were above or below 50 years of age. A variance analysis was performed to compare the XCI pattern between symptomatic and asymptomatic carriers. The results show that 20% of EDMD1 carriers had cardiac symptoms, and that 50% of these were ≥50 years of age. The XCI pattern was similar in both symptomatic and asymptomatic carriers. Conclusions: Arrhythmias in EDMD1 carriers poorly correlate on lymphocytes to a skewed XCI, probably due to (a) the different embryological origin of cardiac conduction tissue compared to lymphocytes or (b) the preferential loss of atrial cells replaced by fibrous tissue.

Spread of X‐chromosome inactivation into autosomal regions in patients with unbalanced X‐autosome translocations and its phenotypic effects

2021 ◽  
Author(s):  
Bianca Pereira Favilla ◽  
Vera Ayres Meloni ◽  
Ana Beatriz Perez ◽  
Danilo Moretti‐Ferreira ◽  
Deise Helena Souza ◽  
...  
Keyword(s):  
X Chromosome ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation

scholarly journals XChromosome Effect on Maternal Recombination and Meiotic Drive in the Mouse

Genetics ◽  
2002 ◽  
Vol 161 (4) ◽  
pp. 1651-1659 ◽  
Author(s):  
Elena de la Casa-Esperón ◽  
J Concepción Loredo-Osti ◽  
Fernando Pardo-Manuel de Villena ◽  
Tammi L Briscoe ◽  
Jan Michel Malette ◽  
...  
Keyword(s):  
Mouse Chromosome ◽  
X Chromosome ◽  
Meiotic Recombination ◽  
Meiotic Drive ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Chromosome 11 ◽  
Genome Wide ◽  
Mouse Chromosome 11 ◽  
Segregation Of Chromosomes

AbstractWe observed that maternal meiotic drive favoring the inheritance of DDK alleles at the Om locus on mouse chromosome 11 was correlated with the X chromosome inactivation phenotype of (C57BL/ 6-Pgk1a × DDK)F1 mothers. The basis for this unexpected observation appears to lie in the well-documented effect of recombination on meiotic drive that results from nonrandom segregation of chromosomes. Our analysis of genome-wide levels of meiotic recombination in females that vary in their X-inactivation phenotype indicates that an allelic difference at an X-linked locus is responsible for modulating levels of recombination in oocytes.

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