Characterization of the central region containing the X-inactivation center and terminal region of the mouse X Chromosome using irradiation and fusion gene transfer hybrids

1991 ◽  
Vol 2 (1) ◽  
pp. 21-31 ◽  
Author(s):  
Louise Sefton ◽  
Danielle Arnaud ◽  
Peter N. Goodfellow ◽  
Marie-Christine Simmler ◽  
Philip Avner
Keyword(s):  
Gene Transfer ◽  
X Chromosome ◽  
Central Region ◽  
Fusion Gene ◽  
Terminal Region ◽  
X Inactivation ◽  
Inactivation Center

Molecular Characterization of Tiny Ring X Chromosomes from Females with Functional X Chromosome Disomy and Lack of cis X Inactivation

Genomics ◽  
1995 ◽  
Vol 27 (1) ◽  
pp. 182-188 ◽  
Author(s):  
Mihir M. Jani ◽  
Beth S. Torchia ◽  
G.Shashidhar Pai ◽  
Barbara R. Migeon
Keyword(s):  
Molecular Characterization ◽  
X Chromosome ◽  
X Inactivation ◽  
X Chromosomes

Getting to the center of X-chromosome inactivation: the role of transgenesThis paper is one of a selection of papers published in this Special Issue, entitled 30th Annual International Asilomar Chromatin and Chromosomes Conference, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 87 (5) ◽  
pp. 759-766 ◽  
Author(s):  
Jakub Minks ◽  
Carolyn J. Brown
Keyword(s):  
X Chromosome ◽  
Peer Review Process ◽  
Regulatory Elements ◽  
X Chromosome Inactivation ◽  
X Inactivation ◽  
Chromosome Inactivation ◽  
Xist Expression ◽  
Inactivation Center ◽  
Xist Rna ◽  
Epigenetic Phenomenon

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.

scholarly journals Functional Analysis of the DXPas34Locus, a 3′ Regulator of Xist Expression

1999 ◽  
Vol 19 (12) ◽  
pp. 8513-8525 ◽  
Author(s):  
E. Debrand ◽  
C. Chureau ◽  
D. Arnaud ◽  
P. Avner ◽  
E. Heard
Keyword(s):  
X Chromosome ◽  
Yeast Artificial Chromosome ◽  
Es Cells ◽  
Artificial Chromosome ◽  
Antisense Transcription ◽  
Regulatory Elements ◽  
X Inactivation ◽  
X Chromosomes ◽  
Inactivation Center ◽  
Controlling Element

ABSTRACT X inactivation in female mammals is controlled by a key locus on the X chromosome, the X-inactivation center (Xic). The Xic controls the initiation and propagation of inactivation in cis. It also ensures that the correct number of X chromosomes undergo inactivation (counting) and determines which X chromosome becomes inactivated (choice). The Xist gene maps to the Xic region and is essential for the initiation of X inactivation in cis. Regulatory elements of X inactivation have been proposed to lie 3′ toXist. One such element, lying 15 kb downstream ofXist, is the DXPas34 locus, which was first identified as a result of its hypermethylation on the active X chromosome and the correlation of its methylation level with allelism at the X-controlling element (Xce), a locus known to affect choice. In this study, we have tested the potential function of theDXPas34 locus in Xist regulation and X-inactivation initiation by deleting it in the context of largeXist-containing yeast artificial chromosome transgenes. Deletion of DXPas34 eliminates both Xistexpression and antisense transcription present in this region in undifferentiated ES cells. It also leads to nonrandom inactivation of the deleted transgene upon differentiation. DXPas34 thus appears to be a critical regulator of Xist activity and X inactivation. The expression pattern of DXPas34 during early embryonic development, which we report here, further suggests that it could be implicated in the regulation of imprintedXist expression.

scholarly journals Mapping of DNA Replication Origins to Noncoding Genes of the X-Inactivation Center

2006 ◽  
Vol 26 (10) ◽  
pp. 3707-3717 ◽  
Author(s):  
Rebecca K. Rowntree ◽  
Jeannie T. Lee
Keyword(s):  
Dna Replication ◽  
X Chromosome ◽  
Epigenetic Regulation ◽  
Cpg Islands ◽  
X Inactivation ◽  
Replication Origins ◽  
Inactivation Center ◽  
Dna Replication Origins ◽  
Choice Location ◽  
Tight Correlation

ABSTRACT In mammals, few DNA replication origins have been identified. Although there appears to be an association between origins and epigenetic regulation, their underlying link to monoallelic gene expression remains unclear. Here, we identify novel origins of DNA replication (ORIs) within the X-inactivation center (Xic). We analyze 86 kb of the Xic using an unbiased approach and find an unexpectedly large number of functional ORIs. Although there has been a tight correlation between ORIs and CpG islands, we find that ORIs are not restricted to CpG islands and there is no dependence on transcriptional activity. Interestingly, these ORIs colocalize to important genetic elements or genes involved in X-chromosome inactivation. One prominent ORI maps to the imprinting center and to a domain within Tsix known to be required for X-chromosome counting and choice. Location and/or activity of ORIs appear to be modulated by removal of specific Xic elements. These data provide a foundation for testing potential relationships between DNA replication and epigenetic regulation in future studies.

Mapping of the distal boundary of the X-inactivation center in a rearranged X chromosome from a female expressing XIST

1993 ◽  
Vol 2 (7) ◽  
pp. 883-887 ◽  
Author(s):  
Kathleen A. Lepplg ◽  
Carolyn J. Brown ◽  
Steven L. Bressler ◽  
Karen Gustashaw ◽  
Roberta A. Pagon ◽  
...  
Keyword(s):  
X Chromosome ◽  
X Inactivation ◽  
Inactivation Center ◽  
Distal Boundary

Molecular characterization of a deleted X chromosome (Xq13.3-Xq21.31) exhibiting random X inactivation

1995 ◽  
Vol 21 (2) ◽  
pp. 113-120 ◽  
Author(s):  
Barbara R. Migeon ◽  
Gail Stetten ◽  
Cathy Tuck-Muller ◽  
Joyce Axelman ◽  
Mihir Jani ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
X Chromosome ◽  
X Inactivation

scholarly journals Clinical Epigenetic Therapies Disrupt Sex Chromosome Dosage Compensation in Human Female Cells

2018 ◽  
Vol 2 (1) ◽  
pp. 2-7 ◽  
Author(s):  
Agnieszka I. Laskowski ◽  
Danielle A. Fanslow ◽  
Erica D. Smith ◽  
Steven T. Kosak
Keyword(s):  
Small Molecule ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Sex Chromosome ◽  
Gene Dosage ◽  
X Inactivation ◽  
Epigenetic Mechanism ◽  
Human Female ◽  
Healthy Human ◽  
Inactivation Center

Sex chromosome gene dosage compensation is required to ensure equivalent levels of X-linked gene expression between males (46, XY) and females (46, XX). To achieve similar expression, X-chromosome inactivation (XCI) is initiated in female cells during early stages of embryogenesis. Within each cell, either the maternal or paternal X chromosome is selected for whole chromosome transcriptional silencing, which is initiated and maintained by epigenetic and chromatin conformation mechanisms. With the emergence of small-molecule epigenetic inhibitors for the treatment of disease, such as cancer, the epigenetic mechanism underlying XCI may be inadvertently targeted. Here, we test 2 small-molecule epigenetic inhibitors being used clinically, GSK126 (a histone H3 lysine 27 methyltransferase inhibitor) and suberoylanilide hydroxamic acid (a histone deacetylase inhibitor), on their effects of the inactive X (Xi) in healthy human female fibroblasts. The combination of these modifiers, at subcancer therapeutic levels, leads to the inability to detect the repressive H3K27me3 modification characteristic of XCI in the majority of the cells. Importantly, genes positioned near the X-inactivation center ( Xic), where inactivation is initiated, exhibit robust expression with treatment of the inhibitors, while genes located near the distal ends of the X chromosome intriguingly exhibit significant downregulation. These results demonstrate that small-molecule epigenetic inhibitors can have profound consequences on XCI in human cells, and they underscore the importance of considering gender when developing and clinically testing small-molecule epigenetic inhibitors, in particular those that target the well-characterized mechanisms of X inactivation.

Isodicentric X chromosome in a patient with Turner syndrome ? implications for localization of the X-inactivation center

1991 ◽  
Vol 87 (4) ◽  
Author(s):  
AnjanaLal Pettigrew ◽  
EdwardR.B. McCabe ◽  
DavidH. Ledbetter ◽  
FrederickF.B. Elder
Keyword(s):  
Turner Syndrome ◽  
X Chromosome ◽  
X Inactivation ◽  
Inactivation Center

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.

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