Controlling elements in the mouse: IV. Evidence of non-random<i>X</i>-inactivation

Johnston, P. G.; Cattanach, B.M.

doi:10.1017/s0016672300020127

Cited by 105 publications

(83 citation statements)

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“…Xce has three well characterized alleles which can be classified as a gradient of strength: Xce c Ͼ Xce b Ͼ Xce a . 45 The heterozygotes exhibit NRXI. Xce maps within or in the vicinity of the Xic (X-chromosome inactivation center), 46 and it has been shown biochemically 45 and cytologically 47 to cause primary NRXI rather than secondary cell selection.…”

Section: Figurementioning

confidence: 99%

“…45 The heterozygotes exhibit NRXI. Xce maps within or in the vicinity of the Xic (X-chromosome inactivation center), 46 and it has been shown biochemically 45 and cytologically 47 to cause primary NRXI rather than secondary cell selection. Furthermore, the effects of different Xce alleles can modify the imprinted preferential inactivation of Xp in extraembryonic tissue.…”

Section: Figurementioning

confidence: 99%

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X-inactivation analysis in the 1990s: promise and potential problems

Busque

Gilliland

1998

Leukemia

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

X-inactivation analysis in the 1990s: promise and potential problems

Busque

Gilliland

1998

Leukemia

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“…Previous experiments have shown that Xce exerts a primary effect on choice, as skewed X inactivation patterns are observed even in embryos isolated soon after X inactivation occurs (Rastan 1982) and because the effect persists even in the face of a selective advantage for one chromosome over the other (Drews et al 1974). Three alleles of Xce have been defined in inbred mouse strains on the basis of their influence on the X inactivation pattern in genetic crosses: a weak allele Xce a (C3H/HeJ, 101/H, A/J, CBA/J and BALB/cByJ), an intermediate allele Xce b (C57BL/6J, DBA/2J and JU/Ct), and a strong allele Xce c (CAST/Ei), although additional alleles are thought to exist in other strains (Cattanach et al 1969;West and Chapman 1978;Johnston and Cattanach 1981;Simmler et al 1993). In Xce heterozygotes, the chromosome carrying the weaker of the two alleles is more likely to be inactivated.…”

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confidence: 99%

Genetic Control of X Chromosome Inactivation in Mice: Definition of the Xce Candidate Interval

et al. 2006

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In early mammalian development, one of the two X chromosomes is silenced in each female cell as a result of X chromosome inactivation, the mammalian dosage compensation mechanism. In the mouse epiblast, the choice of which chromosome is inactivated is essentially random, but can be biased by alleles at the X-linked X controlling element (Xce). Although this locus was first described nearly four decades ago, the identity and precise genomic localization of Xce remains elusive. Within the X inactivation center region of the X chromosome, previous linkage disequilibrium studies comparing strains of known Xce genotypes have suggested that Xce is physically distinct from Xist, although this has not yet been established by genetic mapping or progeny testing. In this report, we used quantitative trait locus (QTL) mapping strategies to define the minimal Xce candidate interval. Subsequent analysis of recombinant chromosomes allowed for the establishment of a maximum 1.85-Mb candidate region for the Xce locus. Finally, we use QTL approaches in an effort to identify additional modifiers of the X chromosome choice, as we have previously demonstrated that choice in Xce heterozygous females is significantly influenced by genetic variation present on autosomes (Chadwick and Willard 2005). We did not identify any autosomal loci with significant associations and thus show conclusively that Xce is the only major locus to influence X inactivation patterns in the crosses analyzed. This study provides a foundation for future analyses into the genetic control of X chromosome inactivation and defines a 1.85-Mb interval encompassing all the major elements of the Xce locus.

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“…Although the assays to determine the Xce QTL were quite different, previous studies have found that the direction of mating either did not affect the ratio (Johnston and Cattanach 1981) or did influence the X inactivation ratios in heterozygous females (Chadwick and Willard 2005). As noted above, the direction of mating did not affect such measurements in our study of Xce heterozygous progeny.…”

Section: Analysis Of Control Micementioning

confidence: 99%

“…On the future active X chromosome, Xist is silenced during XCI. In mice, Lee and colleagues identified an antisense regulator of Xist, Tsix, whose product is also a noncoding RNA .Tsix expression represses Xist in cis and was shown to be involved in the choice process (Lee and Lu 1999 (Cattanach and Williams 1972;West and Chapman 1978;Johnston and Cattanach 1981). In heterozygous Xce a /Xce c mice, for example, the X inactivation ratio is approximately 0.25, reflecting that 25% of cells will have an active X chromosome with the Xce a allele and 75% of the cells will have an active X chromosome with the Xce c allele (Plenge et al 2000).…”

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Nonrandom X Chromosome Inactivation Is Influenced by Multiple Regions on the Murine X Chromosome

et al. 2012

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During the development of female mammals, one of the two X chromosomes is inactivated, serving as a dosagecompensation mechanism to equalize the expression of X-linked genes in females and males. While the choice of which X chromosome to inactivate is normally random, X chromosome inactivation can be skewed in F1 hybrid mice, as determined by alleles at the X chromosome controlling element (Xce), a locus defined genetically by Cattanach over 40 years ago. Four Xce alleles have been defined in inbred mice in order of the tendency of the X chromosome to remain active: Xce a , Xce b , Xce c , Xce d . While the identity of the Xce locus remains unknown, previous efforts to map sequences responsible for the Xce effect in hybrid mice have localized the Xce to candidate regions that overlap the X chromosome inactivation center (Xic), which includes the Xist and Tsix genes. Here, we have intercrossed 129S1/SvImJ, which carries the Xce a allele, and Mus musculus castaneus EiJ, which carries the Xce c allele, to generate recombinant lines with single or double recombinant breakpoints near or within the Xce candidate region. In female progeny of 129S1/ SvImJ females mated to recombinant males, we have measured the X chromosome inactivation ratio using allele-specific expression assays of genes on the X chromosome. We have identified regions, both proximal and distal to Xist/Tsix, that contribute to the choice of which X chromosome to inactivate, indicating that multiple elements on the X chromosome contribute to the Xce. IN female mammals, either one of the two X chromosomes becomes inactivated during development of the embryo. This random form of X chromosome inactivation (XCI) was first proposed by Lyon (1961) to explain the mosaic pattern of X-linked phenotypes observed in coats of various mammals. XCI serves as a dosage-compensation mechanism to equalize the expression of most X-linked genes in females and males. The steps to random XCI during development of the embryonic lineage are thought to include counting of the number of X chromosomes and the choice of which will be active or inactive, followed by initiation, spreading and finally maintenance of the inactive state throughout development (Heard et al. 1997;Wutz 2011). While choice of which X to inactivate is known to be a primary event occurring early in development, when one X chromosome carries a detrimental mutation, preferential inactivation of the X chromosome with the mutation is typically observed (Morey and Avner 2010). This form of skewed XCI is exemplified in human cells and is most likely due to a secondary cell survival effect in choice (Puck and Willard 1998;Amos-Landgraf et al. 2006). In mice, random XCI is observed in homozygous females carrying X chromosomes from the same genetic background, whereas skewed XCI can be observed when females are heterozygous for X chromosomes from different backgrounds. In contrast to the situation observed in many human females, the process of this skewed XCI in mice is considered to be a primary event in t...

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Controlling elements in the mouse: IV. Evidence of non-randomX-inactivation

Cited by 105 publications

References 34 publications

X-inactivation analysis in the 1990s: promise and potential problems

X-inactivation analysis in the 1990s: promise and potential problems

Genetic Control of X Chromosome Inactivation in Mice: Definition of the Xce Candidate Interval

Nonrandom X Chromosome Inactivation Is Influenced by Multiple Regions on the Murine X Chromosome

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