An extra maternally derived X chromosome is deleterious to early mouse development

Development ◽  
1990 ◽  
Vol 110 (3) ◽  
pp. 969-975 ◽  
Author(s):  
C. Shao ◽  
N. Takagi
Keyword(s):  
X Chromosome ◽  
Early Death ◽  
X Inactivation ◽  
Mouse Development ◽  
Extra Copy ◽  
X Chromosomes ◽  
Extraembryonic Membranes ◽  
Early Mouse ◽  
Ectoplacental Cone ◽  
Embryonic Death

An extra copy of the X chromosome, unlike autosomes, exerts only minor effects on development in mammals including man and mice, because all X chromosomes except one are genetically inactivated. Contrary to this contention, we found that an additional maternally derived X (XM) chromosome, but probably not a paternally derived one (XP), consistently contributes to early death of 41,XXY and 41,XXX embryos in mice. Because of imprinted resistance to inactivation, two doses of XM remain active in the trophectoderm, and seem to be responsible for the failure in the development of the ectoplacental cone and extraembryonic ectoderm, and hence, from early embryonic death. Discordant observations in man indicating viability of XMXMXP and XMXMY individuals suggest that imprinting on the human X chromosome is either weak, unstable or erased before the initiation of X-inactivation in progenitors of extraembryonic membranes.

Detrimental effects of two active X chromosomes on early mouse development

Development ◽  
1990 ◽  
Vol 109 (1) ◽  
pp. 189-201 ◽  
Author(s):  
N. Takagi ◽  
K. Abe
Keyword(s):  
X Chromosome ◽  
Distal Segment ◽  
Translocation Chromosome ◽  
Mouse Development ◽  
X Chromosomes ◽  
Developmental Abnormalities ◽  
Inactivation Center ◽  
Normal Males ◽  
Early Mouse ◽  
Embryonic Ectoderm

Matings between female mice carrying Searle's translocation, T(X;16)16H, and normal males give rise to chromosomally unbalanced zygotes with two complete sets of autosomes, one normal X chromosome and one X16 translocation chromosome (XnX16 embryos). Since X chromosome inactivation does not occur in these embryos, probably due to the lack of the inactivation center on X16, XnX16 embryos are functionally disomic for the proximal 63% of the X chromosome and trisomic for the distal segment of chromosome 16. Developmental abnormalities found in XnX16 embryos include: (1) growth retardation detected as early as stage 9, (2) continual loss of embryonic ectoderm cells either by death or by expulsion into the proamniotic cavity, (3) underdevelopment of the ectoplacental cone throughout the course of development, (4) very limited, if any, mesoderm formation, (5) failure in early organogenesis including the embryo, amnion, chorion and yolk sac. Death occurred at 10 days p.c. Since the combination of XO and trisomy 16 does not severely affect early mouse development, it is likely that regulatory mechanisms essential for early embryogenesis do not function correctly in XnX16 embryos due to activity of the extra X chromosome segment of X16.

Preferential paternal X inactivation in extraembryonic tissues of early mouse embryos

Development ◽  
1982 ◽  
Vol 67 (1) ◽  
pp. 127-135
Author(s):  
Mary I. Harper ◽  
Mandy Fosten ◽  
Marilyn Monk
Keyword(s):  
X Chromosome ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Phosphoglycerate Kinase ◽  
X Inactivation ◽  
Preferential Expression ◽  
Trophoblastic Cells ◽  
Extraembryonic Membranes ◽  
Early Mouse

The preferential expression of the maternal X chromosome seen in certain extraembryonic membranes of the mouse was studied by investigating the tissues from which these membranes are derived during early development. The electrophoretic variant of the X-coded enzyme PGK-1 (phosphoglycerate kinase) was used to distinguish the expression of the maternal from the paternal X chromosome in heterozygous females. Both the extraembryonic ectoderm and primary endoderm of 6½-day female egg cylinders gave almost exclusive expression of the maternal form of the enzyme whereas the epiblast gave near equal expression of the two parental alleles. No paternal PGK-1 band could be detected in samples of pooled 3½-day blastocysts, but after 3 or 4 days of culture in vitro a faint paternal band was seen in the resultant outgrowths. The activity of the maternal band in these latter samples had increased greatly from that of the blastocysts, consistent with preferential expression of the maternal Pgk-1 allele in the trophoblastic cells of the outgrowths, while both alleles are expressed in inner-cell-mass cells. The results strongly support the idea that non-random X-chromosome expression is due to preferential paternal X inactivation in trophectoderm (from which extraembryonic ectoderm is derived) and in primary endoderm, and not to cell selection.

Histone macroH2A1 is concentrated in the inactive X chromosome of female preimplantation mouse embryos

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2283-2289 ◽  
Author(s):  
C. Costanzi ◽  
P. Stein ◽  
D.M. Worrad ◽  
R.M. Schultz ◽  
J.R. Pehrson
Keyword(s):  
X Chromosome ◽  
Hybrid Structure ◽  
X Inactivation ◽  
Preimplantation Embryos ◽  
Histone H2a ◽  
Mouse Development ◽  
X Chromosomes ◽  
Inactive X Chromosome ◽  
Preimplantation Mouse Embryos ◽  
Preimplantation Mouse

MacroH2As are core histone proteins with a hybrid structure consisting of a domain that closely resembles a full-length histone H2A followed by a large nonhistone domain. We recently showed that one of the macroH2A subtypes, macroH2A1.2, is concentrated in the inactive X chromosome in adult female mammals. Here we examine the timing of the association of macroH2A1.2 with the inactive X chromosome during preimplantation mouse development in order to assess the possibility that macroH2A1 participates in the initiation of X inactivation. The association of macroH2A1.2 with one of the X chromosomes was observed in 50% of blastocysts, occurring mostly, if not exclusively, in extraembryonic cells as was expected from previous studies, which indicated that X inactivation in embryonic lineages happens after implantation. Examination of earlier embryonic stages indicates that the association of macroH2A1 with the inactive X chromosome begins between the 8- and 16-cell stages. Of the changes that are known to happen during X inactivation in preimplantation embryos, the accumulation of macroH2A1 appears to be the earliest marker of the inactive X chromosome and is the only change that has been shown to occur during the period when transcriptional silencing is initiated.

scholarly journals Live imaging of X chromosome reactivation dynamics in early mouse development can discriminate naïve from primed pluripotent stem cells

Development ◽  
2016 ◽  
Vol 143 (16) ◽  
pp. 2958-2964 ◽  
Author(s):  
Shin Kobayashi ◽  
Yusuke Hosoi ◽  
Hirosuke Shiura ◽  
Kazuo Yamagata ◽  
Saori Takahashi ◽  
...  
Keyword(s):  
Stem Cells ◽  
X Chromosome ◽  
Pluripotent Stem Cells ◽  
Live Imaging ◽  
Mouse Development ◽  
Early Mouse

scholarly journals Human Genes Escaping X-inactivation Revealed by Single Cell Expression Data

2018 ◽  
Author(s):  
Kerem Wainer Katsir ◽  
Michal Linial
Keyword(s):  
Single Cell ◽  
X Chromosome ◽  
Noncoding Rna ◽  
Phenotypic Variability ◽  
Cell Types ◽  
X Inactivation ◽  
Specific Expression ◽  
X Chromosomes ◽  
Human Genes ◽  
Cumulative Knowledge

AbstractBackgroundIn mammals, sex chromosomes pose an inherent imbalance of gene expression between sexes. In each female somatic cell, random inactivation of one of the X-chromosomes restores this balance. While most genes from the inactivated X-chromosome are silenced, 15-25% are known to escape X-inactivation (termed escapees). The expression levels of these genes are attributed to sex-dependent phenotypic variability.ResultsWe used single-cell RNA-Seq to detect escapees in somatic cells. As only one X-chromosome is inactivated in each cell, the origin of expression from the active or inactive chromosome can be determined from the variation of sequenced RNAs. We analyzed primary, healthy fibroblasts (n=104), and clonal lymphoblasts with sequenced parental genomes (n=25) by measuring the degree of allelic-specific expression (ASE) from heterozygous sites. We identified 24 and 49 candidate escapees, at varying degree of confidence, from the fibroblast and lymphoblast transcriptomes, respectively. We critically test the validity of escapee annotations by comparing our findings with a large collection of independent studies. We find that most genes (66%) from the unified set were previously reported as escapees. Furthermore, out of the overlooked escapees, 11 are long noncoding RNA (lncRNAs).ConclusionsX-chromosome inactivation and escaping from it are robust, permanent phenomena that are best studies at a single-cell resolution. The cumulative information from individual cells increases the potential of identifying escapees. Moreover, despite the use of a limited number of cells, clonal cells (i.e., same X-chromosomes are coordinately inhibited) with genomic phasing are valuable for detecting escapees at high confidence. Generalizing the method to uncharacterized genomic loci resulted in lncRNAs escapees which account for 20% of the listed candidates. By confirming genes as escapees and propose others as candidates from two different cell types, we contribute to the cumulative knowledge and reliability of human escapees.

Regulation of imprinted X-chromosome inactivation in mice by Tsix

Development ◽  
2001 ◽  
Vol 128 (8) ◽  
pp. 1275-1286 ◽  
Author(s):  
T. Sado ◽  
Z. Wang ◽  
H. Sasaki ◽  
E. Li
Keyword(s):  
X Chromosome ◽  
X Chromosome Inactivation ◽  
X Inactivation ◽  
Chromosome Inactivation ◽  
Maternal Allele ◽  
Xist Expression ◽  
Developmental Defects ◽  
X Chromosomes ◽  
Embryonic Tissues ◽  
Early Embryonic Lethality

In mammals, X-chromosome inactivation is imprinted in the extra-embryonic lineages with paternal X chromosome being preferentially inactivated. In this study, we investigate the role of Tsix, the antisense transcript from the Xist locus, in regulation of Xist expression and X-inactivation. We show that Tsix is transcribed from two putative promoters and its transcripts are processed. Expression of Tsix is first detected in blastocysts and is imprinted with only the maternal allele transcribed. The imprinted expression of Tsix persists in the extra-embryonic tissues after implantation, but is erased in embryonic tissues. To investigate the function of Tsix in X-inactivation, we disrupted Tsix by insertion of an IRES(β)geo cassette in the second exon, which blocked transcripts from both promoters. While disruption of the paternal Tsix allele has no adverse effects on embryonic development, inheritance of a disrupted maternal allele results in ectopic Xist expression and early embryonic lethality, owing to inactivation of both X chromosomes in females and single X chromosome in males. Further, early developmental defects of female embryos with maternal transmission of Tsix mutation can be rescued by paternal inheritance of the Xist deletion. These results provide genetic evidence that Tsix plays a crucial role in maintaining Xist silencing in cis and in regulation of imprinted X-inactivation in the extra-embryonic tissues.

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

scholarly journals X-chromosome upregulation is dynamically linked to the X-inactivation state

2020 ◽  
Author(s):  
Antonio Lentini ◽  
Christos Coucoravas ◽  
Nathanael Andrews ◽  
Martin Enge ◽  
Qiaolin Deng ◽  
...  
Keyword(s):  
Stem Cells ◽  
X Chromosome ◽  
Embryonic Stem ◽  
Mrna Levels ◽  
X Chromosomes ◽  
Dosage Balance ◽  
Mechanistic Basis ◽  
Early Mouse ◽  
Key Events

AbstractMammalian X-chromosome dosage balance is regulated by X-chromosome inactivation (XCI) and X-chromosome upregulation (XCU), but the dynamics of XCU as well as the interplay between the two mechanisms remain poorly understood. Here, we mapped XCU throughout early mouse embryonic development at cellular and allelic resolution, revealing sex- and lineage-specific dynamics along key events in X-chromosome regulation. Our data show that XCU is linearly proportional to the degree of XCI, indicating that dosage compensation ensues based on mRNA levels rather than number of active X chromosomes. In line with this, we reveal that the two active X chromosomes in female naïve embryonic stem cells are not hyperactive as previously thought. In all lineages, XCU was underlain by increased transcriptional burst frequencies, providing a mechanistic basis in vivo. Together, our results demonstrate unappreciated flexibility of XCU in balancing X-chromosome expression, and we propose a general model for allelic dosage balance, applicable for wider mechanisms of transcriptional regulation.

scholarly journals Studies on Metatherian Sex Chromosomes III. The Use of Tritiated Uridine-induced Chromosome Aberrations to Distinguish Active and Inactive X Chromosomes

1977 ◽  
Vol 30 (2) ◽  
pp. 103 ◽  
Author(s):  
Jennifer A Donald ◽  
DW Cooper
Keyword(s):  
X Chromosome ◽  
Sex Chromosomes ◽  
Chromosome Aberrations ◽  
X Inactivation ◽  
Facultative Heterochromatin ◽  
Hybrid Female ◽  
X Chromosomes ◽  
Toxicity Effect ◽  
Red Kangaroo ◽  
Chromosome Regions

The paternal X inactivation system of kangaroos has been investigated in this study by using tritiated uridine-induced chromosome aberrations to distinguish the active from the inactive X. Previous work in eutherian mammals has demonstrated that constitutive heterochromatic chromosome regions are less susceptible to breakage by tritiated uri dine than euchromatic regions. The results of a comparison between the paternal X chromosome of a wallaroo x red kangaroo hybrid female and the two X chromosomes of a red kangaroo female suggested that the facultative heterochromatin of the X is also less susceptible to breakage by this treatment. However there were significantly more breaks of the paternal X in fibroblasts than in lymphocytes of the hybrid female, which agrees with biochemical findings suggesting activation of the paternal X in fibroblasts. Our results strengthen the suggestion of other workers that the reduced number of aberrations in heterochromatin occurs because such breaks occur principally when the DNA and labelled RNA are in apposition during transcription. Some evidence was found of an apparent toxicity effect of the tritiated uridine solution on the cells.

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