Data for identification of porcine X-chromosome inactivation center, XIC, by genomic comparison with human and mouse XIC

X-chromosome inactivation is a fascinating epigenetic phenomenon that is initiated by expression of a noncoding (nc)RNA, XIST, and results in transcriptional silencing of 1 female X. The process requires a series of events that begins even before XIST expression, and culminates in an active and a silent X within the same nucleus. We will focus on the role that transgenic systems have served in the current understanding of the process of X-chromosome inactivation, both in the initial delineation of an active and inactive X, and in the function of the XIST RNA. X inactivation is strictly cis-limited; recent studies have revealed elements within the X-inactivation center, the region required for inactivation, that are critical for the initial regulation of Xist expression and chromosome pairing. It has been revealed that the X-inactivation center contains a remarkable compendium of cis-regulatory elements, ncRNAs, and trans-acting pairing regions. We review the functional componentry of the X-inactivation center and discuss experiments that helped to dissect the XIST/Xist RNA and its involvement in the establishment of facultative heterochromatin.

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Do LINEs Have a Role in X-Chromosome Inactivation?

Journal of Biomedicine and Biotechnology ◽

10.1155/jbb/2006/59746 ◽

2006 ◽

Vol 2006 ◽

pp. 1-6 ◽

Cited By ~ 19

Author(s):

Mary F. Lyon

Keyword(s):

X Chromosome ◽

X Chromosome Inactivation ◽

Chromosome Inactivation ◽

Current Evidence ◽

X Chromosomes ◽

Repeat Elements ◽

Sequencing Project ◽

Human Genome Sequencing ◽

Human And Mouse

There is longstanding evidence that X-chromosome inactivation (XCI) travels less successfully in autosomal than in X-chromosomal chromatin. The interspersed repeat elements LINE1s (L1s) have been suggested as candidates for “boosters” which promote the spread of XCI in the X-chromosome. The present paper reviews the current evidence concerning the possible role of L1s in XCI. Recent evidence, accruing from the human genome sequencing project and other sources, confirms that mammalian X-chromosomes are indeed rich in L1s, except in regions where there are many genes escaping XCI. The density of L1s is the highest in the evolutionarily oldest regions. Recent work on X; autosome translocations in human and mouse suggested failure of stabilization of XCI in autosomal material, so that genes are reactivated, but resistance of autosomal genes to the original silencing is not excluded. The accumulation of L1s on the X-chromosome may have resulted from reduced recombination or late replication. Whether L1s are part of the mechanism of XCI or a result of it remains enigmatic.

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Replication origin activity in vole X chromosome inactivation center in different cell types

Doklady Biochemistry and Biophysics ◽

10.1134/s1607672913030125 ◽

2013 ◽

Vol 450 (1) ◽

pp. 164-166

Author(s):

V. V. Sherstyuk ◽

A. I. Shevchenko ◽

N. A. Mazurok ◽

S. M. Zakian

Keyword(s):

X Chromosome ◽

Replication Origin ◽

Cell Types ◽

X Chromosome Inactivation ◽

Chromosome Inactivation ◽

Inactivation Center ◽

Different Cell Types

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

International Journal of Molecular Sciences ◽

10.3390/ijms23020611 ◽

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.

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Epigenetic-structural changes in X chromosomes promote Xic pairing during early differentiation from mouse embryonic stem cells

10.1101/2021.10.25.465811 ◽

2021 ◽

Author(s):

Tetsushi Komoto ◽

Masashi Fujii ◽

Akinori Awazu

Keyword(s):

X Chromosome ◽

Structural Changes ◽

Es Cells ◽

Embryonic Stem ◽

X Chromosome Inactivation ◽

Chromosome Inactivation ◽

Coarse Grained ◽

Dynamics Model ◽

X Chromosomes ◽

Inactivation Center

X chromosome inactivation center (Xic) pairing is robustly observed during the differentiation of embryonic stem (ES) cells from female mouse embryos, and this process is related to X chromosome inactivation, the circadian clock, intra-nucleus architecture, and metabolism. However, the mechanisms underlying the identification and approach of X chromosome pairs in the crowded nucleus are unclear. To elucidate the driving force of Xic pairing, we developed a coarse-grained molecular dynamics model of intranuclear chromosomes in ES cells and in cells 2 days after the onset of differentiation (2-days cells) by considering intrachromosome epigenetic-structural feature-dependent mechanics. The analysis of the experimental data showed X-chromosomes change to specifically softer than autosomes during the cell differentiation by the rearrangement of their distributions of open-close chromatin regions, and the simulations of these models exhibited such softening promoted the mutual approach of the Xic pair. These findings suggested that local intrachromosomal epigenetic features may contribute to the regulation of cell species-dependent differences in intranuclear architecture.

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Cross-species examination of X-chromosome inactivation highlights domains of escape from silencing

Epigenetics & Chromatin ◽

10.1186/s13072-021-00386-8 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Bradley P. Balaton ◽

Oriol Fornes ◽

Wyeth W. Wasserman ◽

Carolyn J. Brown

Keyword(s):

X Chromosome ◽

Cpg Islands ◽

Enrichment Analysis ◽

Regulatory Elements ◽

X Chromosome Inactivation ◽

Chromosome Inactivation ◽

Ctcf Binding ◽

Dna Repeats ◽

Level Control ◽

Human And Mouse

Abstract Background X-chromosome inactivation (XCI) in eutherian mammals is the epigenetic inactivation of one of the two X chromosomes in XX females in order to compensate for dosage differences with XY males. Not all genes are inactivated, and the proportion escaping from inactivation varies between human and mouse (the two species that have been extensively studied). Results We used DNA methylation to predict the XCI status of X-linked genes with CpG islands across 12 different species: human, chimp, bonobo, gorilla, orangutan, mouse, cow, sheep, goat, pig, horse and dog. We determined the XCI status of 342 CpG islands on average per species, with most species having 80–90% of genes subject to XCI. Mouse was an outlier, with a higher proportion of genes subject to XCI than found in other species. Sixteen genes were found to have discordant X-chromosome inactivation statuses across multiple species, with five of these showing primate-specific escape from XCI. These discordant genes tended to cluster together within the X chromosome, along with genes with similar patterns of escape from XCI. CTCF-binding, ATAC-seq signal and LTR repeats were enriched at genes escaping XCI when compared to genes subject to XCI; however, enrichment was only observed in three or four of the species tested. LINE and DNA repeats showed enrichment around subject genes, but again not in a consistent subset of species. Conclusions In this study, we determined XCI status across 12 species, showing mouse to be an outlier with few genes that escape inactivation. Inactivation status is largely conserved across species. The clustering of genes that change XCI status across species implicates a domain-level control. In contrast, the relatively consistent, but not universal correlation of inactivation status with enrichment of repetitive elements or CTCF binding at promoters demonstrates gene-based influences on inactivation state. This study broadens enrichment analysis of regulatory elements to species beyond human and mouse.

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