A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome

Nature ◽  
1991 ◽  
Vol 349 (6304) ◽  
pp. 38-44 ◽  
Author(s):  
Carolyn J. Brown ◽  
Andrea Ballabio ◽  
James L. Rupert ◽  
Ronald G. Lafreniere ◽  
Markus Grompe ◽  
...  
Keyword(s):  
X Chromosome ◽  
X Inactivation ◽  
Inactive X Chromosome

scholarly journals Developmentally regulated alterations in Polycomb repressive complex 1 proteins on the inactive X chromosome

2004 ◽  
Vol 167 (6) ◽  
pp. 1025-1035 ◽  
Author(s):  
Kathrin Plath ◽  
Dale Talbot ◽  
Karien M. Hamer ◽  
Arie P. Otte ◽  
Thomas P. Yang ◽  
...  
Keyword(s):  
X Chromosome ◽  
Protein Complexes ◽  
Histone H3 ◽  
X Inactivation ◽  
Polycomb Group ◽  
Epigenetic Mark ◽  
Embryonic Cells ◽  
Developmentally Regulated ◽  
Inactive X Chromosome ◽  
Multistep Process

Polycomb group (PcG) proteins belonging to the polycomb (Pc) repressive complexes 1 and 2 (PRC1 and PRC2) maintain homeotic gene silencing. In Drosophila, PRC2 methylates histone H3 on lysine 27, and this epigenetic mark facilitates recruitment of PRC1. Mouse PRC2 (mPRC2) has been implicated in X inactivation, as mPRC2 proteins transiently accumulate on the inactive X chromosome (Xi) at the onset of X inactivation to methylate histone H3 lysine 27 (H3-K27). In this study, we demonstrate that mPRC1 proteins localize to the Xi, and that different mPRC1 proteins accumulate on the Xi during initiation and maintenance of X inactivation in embryonic cells. The Xi accumulation of mPRC1 proteins requires Xist RNA and is not solely regulated by the presence of H3-K27 methylation, as not all cells that exhibit this epigenetic mark on the Xi show Xi enrichment of mPRC1 proteins. Our results implicate mPRC1 in X inactivation and suggest that the regulated assembly of PcG protein complexes on the Xi contributes to this multistep process.

scholarly journals When the Lyon(ized chromosome) roars: ongoing expression from an inactive X chromosome

2017 ◽  
Vol 372 (1733) ◽  
pp. 20160355 ◽  
Author(s):  
Laura Carrel ◽  
Carolyn J. Brown
Keyword(s):  
X Chromosome ◽  
X Chromosome Inactivation ◽  
X Inactivation ◽  
Chromosome Inactivation ◽  
Sequencing Technologies ◽  
Inactive X Chromosome ◽  
Underlying Basis ◽  
Inactivation Process ◽  
Escape From X Inactivation ◽  
Mary Lyon

A tribute to Mary Lyon was held in October 2016. Many remarked about Lyon's foresight regarding many intricacies of the X-chromosome inactivation process. One such example is that a year after her original 1961 hypothesis she proposed that genes with Y homologues should escape from X inactivation to achieve dosage compensation between males and females. Fifty-five years later we have learned many details about these escapees that we attempt to summarize in this review, with a particular focus on recent findings. We now know that escapees are not rare, particularly on the human X, and that most lack functionally equivalent Y homologues, leading to their increasingly recognized role in sexually dimorphic traits. Newer sequencing technologies have expanded profiling of primary tissues that will better enable connections to sex-biased disorders as well as provide additional insights into the X-inactivation process. Chromosome organization, nuclear location and chromatin environments distinguish escapees from other X-inactivated genes. Nevertheless, several big questions remain, including what dictates their distinct epigenetic environment, the underlying basis of species differences in escapee regulation, how different classes of escapees are distinguished, and the roles that local sequences and chromosome ultrastructure play in escapee regulation. This article is part of the themed issue ‘X-chromosome inactivation: a tribute to Mary Lyon’.

scholarly journals Structural aspects of the inactive X chromosome

2017 ◽  
Vol 372 (1733) ◽  
pp. 20160357 ◽  
Author(s):  
Giancarlo Bonora ◽  
Christine M. Disteche
Keyword(s):  
X Chromosome ◽  
High Throughput Sequencing ◽  
Nuclear Periphery ◽  
Three Dimensional ◽  
Super Resolution ◽  
Structural Difference ◽  
X Inactivation ◽  
Striking Difference ◽  
Inactive X Chromosome ◽  
Mary Lyon

A striking difference between male and female nuclei was recognized early on by the presence of a condensed chromatin body only in female cells. Mary Lyon proposed that X inactivation or silencing of one X chromosome at random in females caused this structural difference. Subsequent studies have shown that the inactive X chromosome (Xi) does indeed have a very distinctive structure compared to its active counterpart and all autosomes in female mammals. In this review, we will recap the discovery of this fascinating biological phenomenon and seminal studies in the field. We will summarize imaging studies using traditional microscopy and super-resolution technology, which revealed uneven compaction of the Xi. We will then discuss recent findings based on high-throughput sequencing techniques, which uncovered the distinct three-dimensional bipartite configuration of the Xi and the role of specific long non-coding RNAs in eliciting and maintaining this structure. The relative position of specific genomic elements, including genes that escape X inactivation, repeat elements and chromatin features, will be reviewed. Finally, we will discuss the position of the Xi, either near the nuclear periphery or the nucleolus, and the elements implicated in this positioning. This article is part of the themed issue ‘X-chromosome inactivation: a tribute to Mary Lyon’.

scholarly journals The Trithorax group protein Ash2l and Saf-A are recruited to the inactive X chromosome at the onset of stable X inactivation

Development ◽  
2010 ◽  
Vol 137 (6) ◽  
pp. 935-943 ◽  
Author(s):  
D. Pullirsch ◽  
R. Hartel ◽  
H. Kishimoto ◽  
M. Leeb ◽  
G. Steiner ◽  
...  
Keyword(s):  
X Chromosome ◽  
X Inactivation ◽  
Trithorax Group ◽  
Inactive X Chromosome ◽  
Group Protein

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.

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.

An X-linked human collagen transgene escapes X inactivation in a subset of cells

Development ◽  
1992 ◽  
Vol 116 (3) ◽  
pp. 687-695
Author(s):  
H. Wu ◽  
R. Fassler ◽  
A. Schnieke ◽  
D. Barker ◽  
K.H. Lee ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
X Chromosome ◽  
Transgene Expression ◽  
Cultured Cells ◽  
X Inactivation ◽  
Small Subset ◽  
Collagen Gene ◽  
Inactive X Chromosome ◽  
Human Collagen

Transgenic mice carrying one complete copy of the human alpha 1(I) collagen gene on the X chromosome (HucII mice) were used to study the effect of X inactivation on transgene expression. By chromosomal in situ hybridization, the transgene was mapped to the D/E region close to the Xce locus, which is the controlling element. Quantitative RNA analyses indicated that transgene expression in homozygous and heterozygous females was about 125% and 62%, respectively, of the level found in hemizygous males. Also, females with Searle's translocation carrying the transgene on the inactive X chromosome (Xi) expressed about 18% transgene RNA when compared to hemizygous males. These results were consistent with the transgene being subject to but partially escaping from X inactivation. Two lines of evidence indicated that the transgene escaped X inactivation or was reactivated in a small subset of cells rather than being expressed at a lower level from the Xi in all cells, (i) None of nine single cell clones carrying the transgene on the Xi transcribed transgene RNA. In these clones the transgene was highly methylated in contrast to clones carrying the transgene on the Xa. (ii) In situ hybridization to RNA of cultured cells revealed that about 3% of uncloned cells with the transgene on the Xi expressed transgene RNA at a level comparable to that on the Xa. Our results indicate that the autosomal human collagen gene integrated on the mouse X chromosome is susceptible to X inactivation. Inactivation is, however, not complete as a subset of cells carrying the transgene on Xi expresses the transgene at a level comparable to that when carried on Xa.

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.

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