scholarly journals Age-related reactivation of an X-linked gene close to the inactivation centre in the mouse

1988 ◽  
Vol 52 (2) ◽  
pp. 151-154 ◽  
Author(s):  
Sheila Brown ◽  
Sohaila Rastan
Keyword(s):  
X Chromosome ◽  
Reciprocal Translocation ◽  
Coat Colour ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Wild Type ◽  
Linked Gene ◽  
Female Mice ◽  
Age Related ◽  
Type Gene

SummaryAge-related reactivation of an X-linked gene which maps close to Xce, the X chromosome inactivation centre, has been observed. In five female mice which carried the X-linked coat colour gene Moblo on the reciprocal translocation T(X;16)16H (Searle's translocation), and the wild-type gene on the normal X chromosome, and therefore expressed the Moblo phenotype due to the non-random inactivation characteristic of Searle's translocation, progressive darkening of the coat was observed as the animals aged. This is due to reactivation of the previously inactivated wild-type gene at the Mo locus on the normal X chromosome. As the Mo locus is located 4 cM distal to Xce, the X chromosome inactivation centre, these observations provide evidence of age-related instability of inactivation of an X-linked gene close to the inactivation centre.

scholarly journals Publisher Correction: Female mice lacking Ftx lncRNA exhibit impaired X-chromosome inactivation and a microphthalmia-like phenotype

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Yusuke Hosoi ◽  
Miki Soma ◽  
Hirosuke Shiura ◽  
Takashi Sado ◽  
Hidetoshi Hasuwa ◽  
...  
Keyword(s):  
X Chromosome ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Female Mice

X chromosome inactivation analysis reveals a difference in the biology of ET patients with JAK2 and CALR mutations

Blood ◽  
2014 ◽  
Vol 124 (13) ◽  
pp. 2091-2093 ◽  
Author(s):  
Christopher Allen ◽  
Jonathan R. Lambert ◽  
David C. Linch ◽  
Rosemary E. Gale
Keyword(s):  
X Chromosome ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Wild Type ◽  
Key Points ◽  
Inactivation Pattern ◽  
Calr Mutations ◽  
Calr Mutation

Key Points In ET, a CALR mutation correlates with a monoclonal X chromosome inactivation pattern, which differs from JAK2V617F mutant disease. The presence of a CALR mutant is associated with suppression of wild-type myelopoiesis.

Wiskott-Aldrich syndrome in a female

Blood ◽  
2002 ◽  
Vol 100 (8) ◽  
pp. 2763-2768 ◽  
Author(s):  
Maxim I. Lutskiy ◽  
Yoji Sasahara ◽  
Dianne M. Kenney ◽  
Fred S. Rosen ◽  
Eileen Remold-O'Donnell
Keyword(s):  
T Cells ◽  
X Chromosome ◽  
Blood Cells ◽  
Mononuclear Cells ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Wild Type ◽  
Wiskott Aldrich Syndrome ◽  
Blood Mononuclear Cells ◽  
Disease Free

Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by thrombocytopenia, eczema, and various degrees of immune deficiency. Carriers of mutated WASP have nonrandom X chromosome inactivation in their blood cells and are disease-free. We report data on a 14-month-old girl with a history of WAS in her family who presented with thrombocytopenia, small platelets, and immunologic dysfunction. Sequencing of the WASP gene showed that the patient was heterozygous for the splice site mutation previously found in one of her relatives with WAS. Sequencing of all WASP exons revealed no other mutation. Levels of WASP in blood mononuclear cells were 60% of normal. Flow cytometry after intracellular staining of peripheral blood mononuclear cells with WASP monoclonal antibody revealed both WASPbright and WASPdimpopulations. X chromosome inactivation in the patient's blood cells was found to be random, demonstrating that both maternal and paternal active X chromosomes are present. These findings indicate that the female patient has a defect in the mechanisms that lead in disease-free WAS carriers to preferential survival/proliferation of cells bearing the active wild-type X chromosome. Whereas the patient's lymphocytes are skewed toward WASPbright cells, about 65% of her monocytes and the majority of her B cells (CD19+) are WASPdim. Her naive T cells (CD3+CD45RA+) include WASPbrightand WASPdim populations, but her memory T cells (CD3+CD45RA−) are all WASPbright. After activation in vitro of T cells, all cells exhibited CD3+CD45RA− phenotype and most were WASPbright with active paternal (wild-type) X chromosome, suggesting selection against the mutated WASP allele during terminal T-cell maturation/differentiation.

scholarly journals Skewness of X-chromosome inactivation increases with age and varies across birth cohorts in elderly Danish women

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jonas Mengel-From ◽  
Rune Lindahl-Jacobsen ◽  
Marianne Nygaard ◽  
Mette Soerensen ◽  
Karen Helene Ørstavik ◽  
...  
Keyword(s):  
X Chromosome ◽  
X Chromosome Inactivation ◽  
X Inactivation ◽  
Chromosome Inactivation ◽  
Chromosomal Mosaicism ◽  
Birth Cohorts ◽  
Cross Sectional ◽  
Time Points ◽  
Age Related ◽  
Skewed X Chromosome Inactivation

AbstractMosaicism in blood varies with age, and cross-sectional studies indicate that for women, skewness of X-chromosomal mosaicism increases with age. This pattern could, however, also be due to less X-inactivation in more recent birth cohorts. Skewed X-chromosome inactivation was here measured longitudinally by the HUMARA assay in 67 septuagenarian and octogenarian women assessed at 2 time points, 10 years apart, and in 10 centenarian women assessed at 2 time points, 2–7 years apart. Skewed X-chromosome inactivation was also compared in 293 age-matched septuagenarian twins born in 1917–1923 and 1931–1937, and 212 centenarians born in 1895, 1905 and 1915. The longitudinal study of septuagenarians and octogenarians revealed that 16% (95% CI 7–29%) of the women developed skewed X-inactivation over a 10-year period. In the cross-sectional across-birth cohort study, the earlier-born septuagenarian (1917–1923) and centenarian women (1895) had a higher degree of skewness than the respective recent age-matched birth cohorts, which indicates that the women in the more recent cohorts, after the age of 70, had not only changed degree of skewness with age, they had also undergone less age-related hematopoietic sub-clone expansion. This may be a result of improved living conditions and better medical treatment in the more recent birth cohorts.

scholarly journals Attempts to test the inactive-X theory of dosage compensation in mammals

1963 ◽  
Vol 4 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Mary F. Lyon
Keyword(s):  
X Chromosome ◽  
Adult Female ◽  
Dosage Compensation ◽  
Somatic Cells ◽  
Coat Colour ◽  
The Other ◽  
Wild Type ◽  
X Chromosomes ◽  
Female Mice ◽  
Colour Mutant

The inactive-X theory of dosage compensation postulates that in all somatic cells of adult female mammals one or other of the two X chromosomes is genetically inactive. This means that in a female heterozygous for two non-allelic genes acting through the same cells, and carried one on each X chromosome, one or other gene should act in all cells. Conversely, if the two genes are carried on the same X, then both genes should act in some cells and neither gene in the remainder. This point has been tested by breeding experiments with mice, using pairs of genes affecting coat colour and coat texture. In female mice carrying the colour mutant dappled, Modp, on one X and a translocation including the wild-type alleles of pink-eye, p, and albino, c, on the other, either Modp or the translocation acted in all cells. With the genes tabby, Ta and striated, Str, affecting coat texture, in Str + / + Ta females tabby acted only in the non-Str patches, while in StrTa/ + + it acted only in the Str ones. Thus these experiments confirm that only one of the two X chromosomes is active in the somatic cells of female mammals.

scholarly journals The lncRNAs at X Chromosome Inactivation Center: Not Just a Matter of Sex Dosage Compensation

2022 ◽  
Vol 23 (2) ◽  
pp. 611
Author(s):  
Chiara Siniscalchi ◽  
Armando Di Palo ◽  
Aniello Russo ◽  
Nicoletta Potenza
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Regulatory Networks ◽  
X Chromosome Inactivation ◽  
X Inactivation ◽  
Chromosome Inactivation ◽  
Linked Gene ◽  
Regulatory Circuit ◽  
Rna Targets ◽  
Inactivation Center

Non-coding RNAs (ncRNAs) constitute the majority of the transcriptome, as the result of pervasive transcription of the mammalian genome. Different RNA species, such as lncRNAs, miRNAs, circRNA, mRNAs, engage in regulatory networks based on their reciprocal interactions, often in a competitive manner, in a way denominated “competing endogenous RNA (ceRNA) networks” (“ceRNET”): miRNAs and other ncRNAs modulate each other, since miRNAs can regulate the expression of lncRNAs, which in turn regulate miRNAs, titrating their availability and thus competing with the binding to other RNA targets. The unbalancing of any network component can derail the entire regulatory circuit acting as a driving force for human diseases, thus assigning “new” functions to “old” molecules. This is the case of XIST, the lncRNA characterized in the early 1990s and well known as the essential molecule for X chromosome inactivation in mammalian females, thus preventing an imbalance of X-linked gene expression between females and males. Currently, literature concerning XIST biology is becoming dominated by miRNA associations and they are also gaining prominence for other lncRNAs produced by the X-inactivation center. This review discusses the available literature to explore possible novel functions related to ceRNA activity of lncRNAs produced by the X-inactivation center, beyond their role in dosage compensation, with prospective implications for emerging gender-biased functions and pathological mechanisms.

95 DOSAGE COMPENSATION OF X CHROMOSOME INACTIVATION CENTER (XIC)-LINKED GENES IS ALREADY ACHIEVED IN PORCINE BLASTOCYST

2015 ◽  
Vol 27 (1) ◽  
pp. 140
Author(s):  
J. Y. Hwang ◽  
J.-N. Oh ◽  
D.-K. Lee ◽  
C.-H. Park ◽  
C.-K. Lee
Keyword(s):  
Dna Methylation ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Cell Biology ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Linked Gene ◽  
Male And Female ◽  
Expression Levels ◽  
Species Specific

X-chromosome inactivation (XCI) is an epigenetically essential process for balancing dosage of X-linked genes between male and female eutherian. Importance of this complex and species-specific event has been highlighted recently in developmental and stem cell biology. However, the process has been confirmed only in restricted species, even though the species-specific studies are needed for comprehensive understanding of XCI in specific species. XCI is regulated by the various genes, many of which are coded on the X chromosome inactivation centre (XIC). Among the XIC-linked genes, especially non-coding RNA (ncRNA) like XIST, which is master gene for XCI, are known to regulate XIC. But the centre is not identified in various species. In this study, we identified XIC in pig and analysed the dosage differences of XIC-linked gene in porcine embryos. At first, the centre was searched in pig. The genomic length of the porcine XIC was similar to human XIC and the order and coding strand of the counterparts in pig XIC were same as the human XIC-linked genes. However, sequence comparison between human XIC-linked gene and its porcine counterpart showed that ncRNA around XIST were less conserved rather than protein-coding genes. This would be caused by rapid evolution of genomic region harboring ncRNA. The expression of XIC-linked genes was compared between male and female porcine embryonic fibroblast (PEF) to confirm that dosage compensation is completed in PEF. Most of the genes were not expressed sex-specifically, but two genes, XIST and an uncharacterized gene, LOC102165544, were expressed female preferentially in PEF. Interestingly, LOC102165544, which had low sequence homology with human JPX, was expressed about 2-fold higher in female PEF. This means that XIST and LOC102165544 are XCI-escaping genes. Among the XIC-linked genes, CHIC1, XIST, LOC102165544, and RLIM were stably expressed in embryonic stage, and XIST and LOC102165544 were up-regulated after morula formation. As XIST accumulation is a requisite for XCI initiation, expression levels of the 4 genes between male and female blastocysts were compared. Interestingly, expression levels of CHIC1 and RLIM were not different in male and female blastocysts. This means their dosage would be already compensated in porcine blastocyst. Additionally, to confirm loci of the 2 genes CHIC1 and RLIM harbor one of the inactive alleles in female blastocyst, the DNA methylation pattern was examined. One of the CHIC1 alleles was inactive but RLIM CpG site was hypo-methylated in female blastocyst. This would indicate that one of the RLIM alleles is transcriptionally inactivated by chromatin modification rather than by DNA methylation of the allele. Regulatory regions of XIST and LOC102165544 were demethylated in blastocyst and this showed XCI was not finished in porcine blastocyst. Conclusively, our results demonstrate the XCI already occurs in porcine blastocyst at least one gene but it is not completed.This work was supported by Next BioGreen21 program (PJ009493), Rural Development Administration, Republic of Korea.

Clonal analysis of X-chromosome inactivation and the origin of the germ line in the mouse embryo

Development ◽  
1985 ◽  
Vol 88 (1) ◽  
pp. 349-363
Author(s):  
R. L. Gardner ◽  
M.F. Lyon ◽  
E. P. Evans ◽  
M.D. Burtenshaw
Keyword(s):  
X Chromosome ◽  
Germ Line ◽  
Cell Clone ◽  
Donor Cell ◽  
Coat Colour ◽  
X Chromosome Inactivation ◽  
X Inactivation ◽  
Chromosome Inactivation ◽  
Parental Origin ◽  
Donor Cells

Cloning of cells from peri-implantation embryos by blastocyst injection was used to investigate the time of X-chromosome inactivation in that part of the ectoderm lineage giving rise to foetal tissues of the mouse. Matings were arranged so that the two X-chromosomes of female donor cells controlled two distinct coat colours and host blastocysts were of a third colour genotype. No coat chimaeras were obtained in experiments using donor cells from the primitive ectoderm of 6th or 7th day embryos or from lactationally delayed implanting or reactivated blastocysts. In contrast, a minimum of 80 unequivocal coat chimaeras were obtained in experiments in which primitive ectoderm cells from 5th day implanting blastocysts were used for injection. The majority of these chimaeras that had received a female cell exhibited both donor colours in addition to host colour in their coats, suggesting that the donor cell had not undergone X-inactivation until one or more cycles after transplantation. The remainder of such chimaeras exhibited only one or other donor coat colour. Determination of the parental origin of the allocyclic X-chromosome in donor metaphase preparations in internal tissues of several chimaeras revealed that the coat pattern did not always reflect the X-activity status of the donor cell clone as a whole. Nevertheless, the findings suggest that X-inactivation takes place shortly after implantation in the primitive ectoderm cell population from which the foetus is derived. Of the 68 chimaeras in which the sex of both the donor and host component was established 62 proved to be fertile. Furthermore, 21 of the 37 fertile chimaeras whose sex corresponded with that of the donor cell yielded functional gametes of donor origin. Injection of cells from a single donor blastocyst into a series of host blastocysts established that at least 2 cells in 5th day primitive ectoderm can give rise to both somatic cells and functional germ cells among their mitotic descendants.

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