Genetic activity of sex chromosomes in somatic cells of mammals

1970 ◽  
Vol 259 (828) ◽  
pp. 41-52 ◽  
Keyword(s):  
X Chromosome ◽  
Germ Cells ◽  
Chromosome Region ◽  
Somatic Cells ◽  
X Inactivation ◽  
X Chromosomes ◽  
Animal Group ◽  
Inactive X Chromosome ◽  
Genetic Activity ◽  
Partial Inactivation

Mammals are thought to have a type of dosage compensation not so far known in any other animal group: however many X chromosomes are present, only one remains genetically active in somatic cells. Considerable evidence for this idea exists, in spite of criticism; the greatest difficulty is presented by the abnormalities in human individuals with X chromosome aberrations. Possible explanations for these abnormalities include: wrong X chromosome dosage in early development before X inactivation, reversal of inactivation, partial inactivation of both X chromosomes, activity of the X while in the condensed inactive state, and the presence of a homologous non-inactivated region of the human X and Y. In female germ cells X inactivation apparently does not occur, but the situation in male germ cells is less clear. The Y chromosome is probably also inactive in somatic cells of adults, but again its function in germ cells is not yet clear. Some species have a presumed doubly inactive X chromosome region, as well as the singly active one. The origins and functions of this region are unknown; it may have a role in female germ cells.

Review Lecture: Mechanisms and evolutionary origins of variable X-chromosome activity in mammals

1974 ◽  
Vol 187 (1088) ◽  
pp. 243-268 ◽  
Keyword(s):  
X Chromosome ◽  
Germ Cells ◽  
Gene Dosage ◽  
Control Mechanisms ◽  
Compensation Mechanism ◽  
X Chromosomes ◽  
Animal Group ◽  
Evolutionary Origins ◽  
Genetic Activity ◽  
Males And Females

The X-chromosome of mammals is remarkable for its variable genetic activity. In somatic cells only a single X-chromosome is active, no matter how many are present, thus providing a dosage compensation mechanism by which males and females effectively have the same gene dosage of X-linked genes. In germ cells, however, it appears that all X-chromosomes present are active. Female germ cells require the presence of two X-chromosomes for normal survival, whereas male germ cells die if they have more than one X-chromosome. This system is found in all eutherian mammals and in marsupials, but is not known in any other animal group. In marsupials the X-chromosome derived from the father seems to be preferentially inactivated, whereas in eutherian mammals that from either parent may be so in different cells of the same animal. The differentiation of a particular X-chromosome as active or inactive is initiated in early embryogeny, and thereafter maintained through all further cell divisions in that individual. The mechanisms by which this is achieved are of great interest in relation to genetic control mechanisms in general. Various recent hypotheses concerning these mechanisms are discussed.

scholarly journals X chromosome activity in female germ cells of mice heterozygous for Searle's translocation T(X;16)16H

1981 ◽  
Vol 37 (3) ◽  
pp. 317-322 ◽  
Author(s):  
P. G. Johnston
Keyword(s):  
X Chromosome ◽  
Germ Cells ◽  
Meiotic Prophase ◽  
Somatic Cells ◽  
Phosphoglycerate Kinase ◽  
Inactive X Chromosome ◽  
Faint Band

SUMMARYThe expression of X-linked phosphoglycerate kinase (PGK-1) in germ cells from embryos heterozygous for both PGK-1 and Searle's translocation T(X; 16) 16H was examined to investigate X chromosome activity during oogenesis. The Pgk-lb allele on the translocated X chromosome was the only allele active in somatic cells of all embryos and in germ cells from 12·5 d.p.c. embryos. However, an additional faint band representing Pgk-la activity was observed in germ cells from older embryos (13·5–18·5 d.p.c.) and neonates (1–2 d.p.p.). It is concluded that there is a period when only one X chromosome is active in early female germ cells and that reactivation of the inactive X chromosome takes place just prior to meiotic prophase.

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 The pattern of X-chromosome inactivation in the embryonic and extra-embryonic tissues of post-implantation digynic triploid LT/Sv strain mouse embryos

1990 ◽  
Vol 56 (2-3) ◽  
pp. 107-114 ◽  
Author(s):  
S. Speirs ◽  
J. M. Cross ◽  
M. H. Kaufman
Keyword(s):  
X Chromosome ◽  
Sex Chromosome ◽  
Yolk Sac ◽  
X Inactivation ◽  
Tissue Samples ◽  
X Chromosomes ◽  
Embryonic Tissues ◽  
Inactive X Chromosome ◽  
Distinct Cell ◽  
Inactivation Pattern

SummarySpontaneously cycling LT/Sv strain female mice were mated to hemizygous Rb(X.2)2Ad males in order to facilitate the distinction of the paternal X chromosome, and the pregnant females were autopsied at about midday on the tenth day of gestation. Out of a total of 222 analysable embryos recovered, 165 (74·3%) were diploid and 57 (25·7%) were triploid. Of the triploids, 26 had an XXY and 31 an XXX sex chromosome constitution. Both embryonic and extra-embryonic tissue samples from the triploids were analysed cytogenetically by G-banding and by the Kanda technique to investigate their X-inactivation pattern. The yolk sac samples were separated enzymatically into their endodermally-derived and mesodermally-derived components, and these were similarly analysed, as were similar samples from a selection of control XmXp diploid embryos. In the case of the XmXmY digynic triploid embryos, a single darkly-staining Xm chromosome was observed in 485 (82·9%) out of 585, 304 (73·3%) out of 415, and 165 (44·7%) out of 369 metaphases from the embryonic, yolk sac mesodermally-derived and yolk sac endodermally-derived tissues, respectively. The absence of a darkly staining X-chromosome in the other metaphase spreads could either indicate that both X-chromosomes present were active, or that the Kanda technique had failed to differentially stain the inactive X-chromosome(s) present. In the case of the XmXmXp digynic triploid embryos, virtually all of the tissues analysed comprised two distinct cell lineages, namely those with two darkly-staining X-chromosomes, and those with a single darkly staining X-chromosome. Four X-inactivation patterns were consequently observed in this group, namely, (XmXp)Xm, (XmXm)Xp, (Xm)XmXp and XmXm(Xp) in which the inactive X is enclosed in parentheses. The incidence of these various classes varied among the tissues analysed. There was, however, a clear pattern of non-random selective paternal X-inactivation in yolk sac endodermally-derived samples which possessed two inactive X-chromosomes. This finding contrasts with the situation observed in the yolk sac mesodermally-derived and embryonic samples which possessed two inactive X-chromosomes, where the ratio of (XmXm)Xp:Xm(XmXp) was 1:1·20 and 1:1·03, respectively, being clear evidence that random X-inactivation had occurred in these tissues.

scholarly journals Evidence of non-random X chromosome activity in the mouse

1972 ◽  
Vol 19 (3) ◽  
pp. 229-240 ◽  
Author(s):  
B. M. Cattanach ◽  
C. E. Williams
Keyword(s):  
X Chromosome ◽  
Female Mouse ◽  
Somatic Cells ◽  
Inbred Strains ◽  
X Inactivation ◽  
Cell Populations ◽  
Alternative States ◽  
X Chromosomes ◽  
Inbred Strains Of Mice ◽  
Controlling Element

SUMMARYX-linked modification of the heterozygous phenotypes of X-linked genes has been detected in the X chromosomes of several inbred strains of mice. The effect is similar to that of the alternative ‘states’ or alleles, of the X chromosome controlling element, Xce, identified in T(1; X)Ct X chromosomes. Tests on two such differing X chromosomes have indicated that the phenotypic modification results either from non-random inactivation of the two X chromosomes or from selection operating on the two cell populations differentiated by X-inactivation. The data provide evidence of non-random X chromosome activity in the somatic cells of the female mouse.

scholarly journals Species-specific differences in X chromosome inactivation in mammals

Reproduction ◽  
2013 ◽  
Vol 146 (4) ◽  
pp. R131-R139 ◽  
Author(s):  
Takashi Sado ◽  
Takehisa Sakaguchi
Keyword(s):  
X Chromosome ◽  
Molecular Basis ◽  
Embryonic Stem ◽  
X Chromosome Inactivation ◽  
X Inactivation ◽  
Chromosome Inactivation ◽  
X Chromosomes ◽  
Inactive X Chromosome ◽  
Species Specific ◽  
Genetically Manipulated

In female mammals, the dosage difference in X-linked genes between XX females and XY males is compensated for by inactivating one of the two X chromosomes during early development. Since the discovery of the X inactive-specific transcript (XIST) gene in humans and its subsequent isolation of the mouse homolog, Xist, in the early 1990s, the molecular basis of X chromosome inactivation (X-inactivation) has been more fully elucidated using genetically manipulated mouse embryos and embryonic stem cells. Studies on X-inactivation in other mammals, although limited when compared with those in the mice, have revealed that, while their inactive X chromosome shares many features with those in the mice, there are marked differences in not only some epigenetic modifications of the inactive X chromosome but also when and how X-inactivation is initiated during early embryonic development. Such differences raise the issue about what extent of the molecular basis of X-inactivation in the mice is commonly shared among others. Recognizing similarities and differences in X-inactivation among mammals may provide further insight into our understanding of not only the evolutionary but also the molecular aspects for the mechanism of X-inactivation. Here, we reviewed species-specific differences in X-inactivation and discussed what these differences may reveal.

X-chromosome activity of the mouse primordial germ cells revealed by the expression of an X-linked lacZ transgene

Development ◽  
1994 ◽  
Vol 120 (10) ◽  
pp. 2925-2932 ◽  
Author(s):  
P.P. Tam ◽  
S.X. Zhou ◽  
S.S. Tan
Keyword(s):  
X Chromosome ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Cell Lineage ◽  
Primitive Streak ◽  
X Inactivation ◽  
Lacz Gene ◽  
Genital Ridge ◽  
X Chromosomes ◽  
Fetal Ovary

We have determined the timing of the inactivation and reactivation of the X chromosome in the mouse primordial germ cells (PGCs) by monitoring the expression of an X-linked HMG-lacZ reporter gene. PGCs were identified by their distinct alkaline phosphatase activity and they were first localised in the primitive streak and allantoic bud of the 7.5-day gastrulating embryo. Although inactivation of the transgene was found in some PGCs at these sites, at least 85% of the population were still expressing the lacZ gene. This suggests that, although X-inactivation has commenced during gastrulation, the majority of PGCs still possess two active X chromosomes. Transgene activity remained unchanged during the relocation of PGCs to the hindgut endoderm, but decreased abruptly when PGCs left the hindgut and migrated through the mesentery. X-inactivation was completed during the migration of PGCs, but not simultaneously for the whole population. The first wave of PGCs entering the genital ridge at 9.5 days did not immediately re-activate the silent transgene until about 24 hours later. Re-activation of the transgene took place in over 80% of PGCs entering the genital ridge at 10.5-13.5 days p.c., preceding the entry into meiosis. About 90% of the meiotic germ cells in the 14.5-15.5 day fetal ovary expressed the transgene. Similar profiles of transgene activity were observed in PGCs of embryos that have inherited the lacZ transgene from different parents, showing unequivocally that X-inactivation in the germ cell lineage is not related to parental legacy.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Stabilization and Localization of Xist RNA are Controlled by Separate Mechanisms and are Not Sufficient for X Inactivation

1998 ◽  
Vol 142 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Christine Moulton Clemson ◽  
Jennifer C. Chow ◽  
Carolyn J. Brown ◽  
Jeanne Bentley Lawrence
Keyword(s):  
X Chromosome ◽  
Somatic Cells ◽  
X Inactivation ◽  
X Chromosomes ◽  
Xist Rna ◽  
Chromosomal Association ◽  
Specific Factors ◽  
Species Specific ◽  
Rna Accumulation ◽  
First Time

These studies address whether XIST RNA is properly localized to the X chromosome in somatic cells where human XIST expression is reactivated, but fails to result in X inactivation (Tinker, A.V., and C.J. Brown. 1998. Nucl. Acids Res. 26:2935–2940). Despite a nuclear RNA accumulation of normal abundance and stability, XIST RNA does not localize in reactivants or in naturally inactive human X chromosomes in mouse/ human hybrid cells. The XIST transcripts are fully stabilized despite their inability to localize, and hence XIST RNA localization can be uncoupled from stabilization, indicating that these are separate steps controlled by distinct mechanisms. Mouse Xist RNA tightly localized to an active X chromosome, demonstrating for the first time that the active X chromosome in somatic cells is competent to associate with Xist RNA. These results imply that species-specific factors, present even in mature, somatic cells that do not normally express Xist, are necessary for localization. When Xist RNA is properly localized to an active mouse X chromosome, X inactivation does not result. Therefore, there is not a strict correlation between Xist localization and chromatin inactivation. Moreover, expression, stabilization, and localization of Xist RNA are not sufficient for X inactivation. We hypothesize that chromosomal association of XIST RNA may initiate subsequent developmental events required to enact transcriptional silencing.

scholarly journals Bipartite structure of the inactive mouse X chromosome

2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Xinxian Deng ◽  
Wenxiu Ma ◽  
Vijay Ramani ◽  
Andrew Hill ◽  
Fan Yang ◽  
...  
Keyword(s):  
X Chromosome ◽  
Structural Changes ◽  
3D Structure ◽  
Boundary Region ◽  
X Inactivation ◽  
Imprinted Genes ◽  
X Chromosomes ◽  
F1 Hybrid ◽  
Inactive X Chromosome ◽  
Single Allele

Abstract Background In mammals, one of the female X chromosomes and all imprinted genes are expressed exclusively from a single allele in somatic cells. To evaluate structural changes associated with allelic silencing, we have applied a recently developed Hi-C assay that uses DNase I for chromatin fragmentation to mouse F1 hybrid systems. Results We find radically different conformations for the two female mouse X chromosomes. The inactive X has two superdomains of frequent intrachromosomal contacts separated by a boundary region. Comparison with the recently reported two-superdomain structure of the human inactive X shows that the genomic content of the superdomains differs between species, but part of the boundary region is conserved and located near the Dxz4/DXZ4 locus. In mouse, the boundary region also contains a minisatellite, Ds-TR, and both Dxz4 and Ds-TR appear to be anchored to the nucleolus. Genes that escape X inactivation do not cluster but are located near the periphery of the 3D structure, as are regions enriched in CTCF or RNA polymerase. Fewer short-range intrachromosomal contacts are detected for the inactive alleles of genes subject to X inactivation compared with the active alleles and with genes that escape X inactivation. This pattern is also evident for imprinted genes, in which more chromatin contacts are detected for the expressed allele. Conclusions By applying a novel Hi-C method to map allelic chromatin contacts, we discover a specific bipartite organization of the mouse inactive X chromosome that probably plays an important role in maintenance of gene silencing.

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