scholarly journals H4K20me1 and H3K27me3 are concurrently loaded onto the inactive X chromosome but dispensable for inducing gene silencing

EMBO Reports ◽  
2021 ◽  
Author(s):  
Sjoerd J D Tjalsma ◽  
Mayako Hori ◽  
Yuko Sato ◽  
Aurelie Bousard ◽  
Akito Ohi ◽  
...  
Keyword(s):  
Gene Silencing ◽  
X Chromosome ◽  
Inactive X Chromosome

Inhibition of Atm and/or Atr disrupts gene silencing on the inactive X chromosome

2005 ◽  
Vol 337 (3) ◽  
pp. 875-880 ◽  
Author(s):  
Yan Ouyang ◽  
Jennifer Salstrom ◽  
Silvia Diaz-Perez ◽  
Shareef Nahas ◽  
Youko Matsuno ◽  
...  
Keyword(s):  
Gene Silencing ◽  
X Chromosome ◽  
Inactive X Chromosome

scholarly journals Megadomains and superloops form dynamically but are dispensable for X-chromosome inactivation and gene escape

2018 ◽  
Author(s):  
John E. Froberg ◽  
Stefan F. Pinter ◽  
Andrea J. Kriz ◽  
Teddy Jégu ◽  
Jeannie T. Lee
Keyword(s):  
Gene Silencing ◽  
X Chromosome ◽  
Nuclear Localization ◽  
Functional Significance ◽  
Xist Expression ◽  
H3k27 Methylation ◽  
3D Genome ◽  
Inactive X Chromosome ◽  
Topologically Associated Domains ◽  
Escape From X Inactivation

ABSTRACTThe mammalian inactive X-chromosome (Xi) is structurally distinct from all other chromosomes and serves as a model for how the 3D genome is organized. The Xi shows weakened topologically associated domains and is instead organized into megadomains and superloops directed by the noncoding loci, Dxz4 and Firre. Their functional significance is presently unclear, though one study suggests that they permit Xi genes to escape silencing. Here, we find that megadomains do not precede Xist expression or Xi gene silencing. Deleting Dxz4 disrupts megadomain formation, whereas deleting Firre weakens intra-megadomain interactions. Surprisingly, however, deleting Dxz4 and Firre has no impact on Xi silencing and gene escape. Nor does it affect Xi nuclear localization, stability, or H3K27 methylation. Additionally, ectopic integration of Dxz4 and Xist is not sufficient to form megadomains on autosomes, further uncoupling megadomain formation from chromosomal silencing. We conclude that Dxz4 and megadomains are dispensable for Xi silencing and escape from X-inactivation.

Uncoupling of X-linked gene silencing from XIST binding by DICER1 and chromatin modulation on human inactive X chromosome

Chromosoma ◽  
2014 ◽  
Vol 124 (2) ◽  
pp. 249-262 ◽  
Author(s):  
Satya Keerthi Kota ◽  
Debabani Roy Chowdhury ◽  
Lakshmi K. Rao ◽  
Venkata Padmalatha ◽  
Lalji Singh ◽  
...  
Keyword(s):  
Gene Silencing ◽  
X Chromosome ◽  
Linked Gene ◽  
Inactive X Chromosome

scholarly journals An Xist-dependent protein assembly mediates Xist localization and gene silencing

2020 ◽  
Author(s):  
Amy Pandya-Jones ◽  
Yolanda Markaki ◽  
Jacques Serizay ◽  
Tsotne Chitiashvilli ◽  
Walter Mancia ◽  
...  
Keyword(s):  
Gene Silencing ◽  
X Chromosome ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Repeat Sequence ◽  
Inactive X Chromosome ◽  
Dependent Protein ◽  
Self Association ◽  
Molecular Forces

SummaryNuclear compartments play diverse roles in regulating gene expression, yet the molecular forces and components driving compartment formation are not well understood. Studying how the lncRNA Xist establishes the inactive-X-chromosome (Xi)-compartment, we found that the Xist RNA-binding-proteins PTBP1, MATR3, TDP43, and CELF1 form a condensate to create an Xi-domain that can be sustained in the absence of Xist. The E-repeat-sequence of Xist serves a multivalent binding-platform for these proteins. Without the E-repeat, Xist initially coats the X-chromosome during XCI onset but subsequently disperses across the nucleus with loss of gene silencing. Recruitment of PTBP1, MATR3, TDP-43 or CELF1 to ΔE-Xist rescues these phenotypes, and requires both self-association of MATR3 and TDP-43 and a heterotypic PTBP1-MATR3-interaction. Together, our data reveal that Xist sequesters itself within the Xi-territory and perpetuates gene silencing by seeding a protein-condensate. Our findings uncover an unanticipated mechanism for epigenetic memory and elucidate the interplay between RNA and RNA-binding-proteins in creating compartments for gene regulation.

scholarly journals Differential activation of the hprt gene on the inactive X chromosome in primary and transformed Chinese hamster cells.

1989 ◽  
Vol 9 (4) ◽  
pp. 1635-1641 ◽  
Author(s):  
S G Grant ◽  
R G Worton
Keyword(s):  
Cell Lines ◽  
X Chromosome ◽  
Gene Activation ◽  
Chinese Hamster ◽  
Fibroblast Cell ◽  
Dna Demethylation ◽  
Hprt Gene ◽  
Primary Fibroblast ◽  
Chinese Hamster Cells ◽  
Inactive X Chromosome

We have investigated the genetic activation of the hprt (hypoxanthine-guanine phosphoribosyltransferase) gene located on the inactive X chromosome in primary and transformed female diploid Chinese hamster cells after treatment with the DNA methylation inhibitor 5-azacytidine (5azaCR). Mutants deficient in HPRT were first selected by growth in 6-thioguanine from two primary fibroblast cell lines and from transformed lines derived from them. These HPRT- mutants were then treated with 5azaCR and plated in HAT (hypoxanthine-methotrexate-thymidine) medium to select for cells that had reexpressed the hprt gene on the inactive X chromosome. Contrary to previous results with primary human cells, 5azaCR was effective in activating the hprt gene in primary Chinese hamster fibroblasts at a low but reproducible frequency of 2 x 10(-6) to 7 x 10(-6). In comparison, the frequency in independently derived transformed lines varied from 1 x 10(-5) to 5 x 10(-3), consistently higher than in the nontransformed cells. This increase remained significant when the difference in growth rates between the primary and transformed lines was taken into account. Treatment with 5azaCR was also found to induce transformation in the primary cell lines but at a low frequency of 4 x 10(-7) to 8 x 10(-7), inconsistent with a two-step model of transformation followed by gene activation to explain the derepression of hprt in primary cells. Thus, these results indicate that upon transformation, the hprt gene on the inactive Chinese hamster X chromosome is rendered more susceptible to action by 5azaCR, consistent with a generalized DNA demethylation associated with the transformation event or with an increase in the instability of an underlying primary mechanism of X inactivation.

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.

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