共查询到20条相似文献,搜索用时 15 毫秒
1.
B F Deys K H Grzeschick A Grzeschick E R Jaffé M Siniscalco 《Science (New York, N.Y.)》1972,175(25):1002-1003
The fibroblasts derived from the skin of a woman heterozygous for an X-linked deficiency of phosphoglycerate kinase represented a mosaic. Two of 22 clones with normal glucose-6-phosphate dehydrogenase activity and hypoxanthine(guanine) phosphoribosyltransferase activity had no phosphoglycerate kinase activity detected by electrophoresis. Because the loci for glucose-6-phosphate dehydrogeniase and hypoxanthine(guanine)phosphoribosyltransferase are already known to undergo inactivation and to be on the short arm of the X chromosome and the locus for phosphoglycerate kinase is on the long arm, these observations support the conclusion that the entire human X chromosome can be involved in X inactivation. 相似文献
2.
Mammalian X inactivation turns off one female X chromosome to enact dosage compensation between XX and XY individuals. X inactivation is known to be regulated in cis by Xite, Tsix, and Xist, but in principle the two Xs must also be regulated in trans to ensure mutually exclusive silencing. Here, we demonstrate that interchromosomal pairing mediates this communication. Pairing occurs transiently at the onset of X inactivation and is specific to the X-inactivation center. Deleting Xite and Tsix perturbs pairing and counting/choice, whereas their autosomal insertion induces de novo X-autosome pairing. Ectopic X-autosome interactions inhibit endogenous X-X pairing and block the initiation of X-chromosome inactivation. Thus, Tsix and Xite function both in cis and in trans. We propose that Tsix and Xite regulate counting and mutually exclusive choice through X-X pairing. 相似文献
3.
C J Epstein 《Science (New York, N.Y.)》1972,175(29):1467-1468
The activity of hypoxanthine-guanine phosphoribosyltransferase in unfertilized mouse ova and in mouse embryos at the two-cell stage is proportional to the number of X chromosomes present during oogenesis. This indicates that the enzyme is X-linked in the mouse and that inactivation of the X chromosome does not occur during oogenesis. However, the genetic dosage effect of the X chromosomes is not present after the increase in hypoxanthine-guanine phosphoribosyltransferase activity in the late morula and the blastocyst stages. These results indicate that the X-linked enzyme lacuts is expressed sometimne after fertilization but before the morula stage. 相似文献
4.
Reactivation of an inactive human X chromosome: evidence for X inactivation by DNA methylation 总被引:88,自引:0,他引:88
A mouse-human somatic cell hybrid clone, deficient in hypoxanthine-guanine phosphoribosyltransferase (HPRT) and containing a structurally normal inactive human X chromosome, was isolated. The hybrid cells were treated with 5-azacytidine and tested for the reactivation and expression of human X-linked genes. The frequency of HPRT-positives clones after 5-azacytidine treatment was 1000-fold greater than that observed in untreated hybrid cells. Fourteen independent HPRT-positive clones were isolated and analyzed for the expression of human X markers. Isoelectric focusing showed that the HPRT expressed in these clones is human. One of the 14 clones expressed human glucose-6-phosphate dehydrogenase and another expressed human phosphoglycerate kinase. Since 5-azacytidine treatment results in hypomethylation of DNA, DNA methylation may be a mechanism of human X chromosome inactivation. 相似文献
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6.
Mammalian sex chromosomes have undergone profound changes since evolving from ancestral autosomes. By examining retroposed genes in the human and mouse genomes, we demonstrate that, during evolution, the mammalian X chromosome has generated and recruited a disproportionately high number of functional retroposed genes, whereas the autosomes experienced lower gene turnover. Most autosomal copies originating from X-linked genes exhibited testis-biased expression. Such export is incompatible with mutational bias and is likely driven by natural selection to attain male germline function. However, the excess recruitment is consistent with a combination of both natural selection and mutational bias. 相似文献
7.
Benos PV Gatt MK Ashburner M Murphy L Harris D Barrell B Ferraz C Vidal S Brun C Demailles J Cadieu E Dreano S Gloux S Lelaure V Mottier S Galibert F Borkova D Minana B Kafatos FC Louis C Sidén-Kiamos I Bolshakov S Papagiannakis G Spanos L Cox S Madueño E de Pablos B Modolell J Peter A Schöttler P Werner M Mourkioti F Beinert N Dowe G Schäfer U Jäckle H Bucheton A Callister DM Campbell LA Darlamitsou A Henderson NS McMillan PJ Salles C Tait EA Valenti P Saunder RD Glover DM 《Science (New York, N.Y.)》2000,287(5461):2220-2222
One of the rewards of having a Drosophila melanogaster whole-genome sequence will be the potential to understand the molecular bases for structural features of chromosomes that have been a long-standing puzzle. Analysis of 2.6 megabases of sequence from the tip of the X chromosome of Drosophila identifies 273 genes. Cloned DNAs from the characteristic bulbous structure at the tip of the X chromosome in the region of the broad complex display an unusual pattern of in situ hybridization. Sequence analysis revealed that this region comprises 154 kilobases of DNA flanked by 1.2-kilobases of inverted repeats, each composed of a 350-base pair satellite related element. Thus, some aspects of chromosome structure appear to be revealed directly within the DNA sequence itself. 相似文献
8.
The genetic linkage map of the human X chromosome 总被引:50,自引:0,他引:50
A database useful for mapping the human X chromosome has been established. The data consist of the genotypic characterizations obtained at more than 20 DNA marker loci from a set of 38 selected families. Multilocus linkage analysis has provided an initial genetic map completely spanning the distance from the distal short arm to the distal long arm of the chromosome, for a total genetic length of at least 185 recombination units. Analysis of the recombinational behavior of fully marked chromosomes suggests that the number of recombination events on the X chromosome may be nonrandom. Linkage studies of six families that carry the mutation which causes Duchenne muscular dystrophy were combined with linkage data from a large number of normal families. This permitted mapping of the locus for Duchenne muscular dystrophy with greater precision and statistical confidence than studies in which disease families alone provided the genotypic database. This observation suggests that the normal linkage map of this chromosome should be especially valuable in the mapping of rare X-linked diseases. 相似文献
9.
Percec I Plenge RM Nadeau JH Bartolomei MS Willard HF 《Science (New York, N.Y.)》2002,296(5570):1136-1139
X chromosome inactivation is the silencing mechanism eutherian mammals use to equalize the expression of X-linked genes between males and females early in embryonic development. In the mouse, genetic control of inactivation requires elements within the X inactivation center (Xic) on the X chromosome that influence the choice of which X chromosome is to be inactivated in individual cells. It has long been posited that unidentified autosomal factors are essential to the process. We have used chemical mutagenesis in the mouse to identify specific factors involved in X inactivation and report two genetically distinct autosomal mutations with dominant effects on X chromosome choice early in embryogenesis. 相似文献
10.
To equalize X-chromosome dosages between the sexes, the female mammal inactivates one of her two X chromosomes. X-chromosome inactivation (XCI) is initiated by expression of Xist, a 17-kb noncoding RNA (ncRNA) that accumulates on the X in cis. Because interacting factors have not been isolated, the mechanism by which Xist induces silencing remains unknown. We discovered a 1.6-kilobase ncRNA (RepA) within Xist and identified the Polycomb complex, PRC2, as its direct target. PRC2 is initially recruited to the X by RepA RNA, with Ezh2 serving as the RNA binding subunit. The antisense Tsix RNA inhibits this interaction. RepA depletion abolishes full-length Xist induction and trimethylation on lysine 27 of histone H3 of the X. Likewise, PRC2 deficiency compromises Xist up-regulation. Therefore, RepA, together with PRC2, is required for the initiation and spread of XCI. We conclude that a ncRNA cofactor recruits Polycomb complexes to their target locus. 相似文献
11.
Reactivation of the paternal X chromosome in early mouse embryos 总被引:2,自引:0,他引:2
Mak W Nesterova TB de Napoles M Appanah R Yamanaka S Otte AP Brockdorff N 《Science (New York, N.Y.)》2004,303(5658):666-669
It is generally accepted that paternally imprinted X inactivation occurs exclusively in extraembryonic lineages of mouse embryos, whereas cells of the embryo proper, derived from the inner cell mass (ICM), undergo only random X inactivation. Here we show that imprinted X inactivation, in fact, occurs in all cells of early embryos and that the paternal X is then selectively reactivated in cells allocated to the ICM. This contrasts with more differentiated cell types where X inactivation is highly stable and generally irreversible. Our observations illustrate that an important component of genome plasticity in early development is the capacity to reverse heritable gene silencing decisions. 相似文献
12.
The initiation of X-chromosome inactivation is thought to be tightly correlated with early differentiation events during mouse development. Here, we show that although initially active, the paternal X chromosome undergoes imprinted inactivation from the cleavage stages, well before cellular differentiation. A reversal of the inactive state, with a loss of epigenetic marks such as histone modifications and polycomb proteins, subsequently occurs in cells of the inner cell mass (ICM), which give rise to the embryo-proper in which random X inactivation is known to occur. This reveals the remarkable plasticity of the X-inactivation process during preimplantation development and underlines the importance of the ICM in global reprogramming of epigenetic marks in the early embryo. 相似文献
13.
Parisi M Nuttall R Naiman D Bouffard G Malley J Andrews J Eastman S Oliver B 《Science (New York, N.Y.)》2003,299(5607):697-700
Sex chromosomes are primary determinants of sexual dimorphism in many organisms. These chromosomes are thought to arise via the divergence of an ancestral autosome pair and are almost certainly influenced by differing selection in males and females. Exploring how sex chromosomes differ from autosomes is highly amenable to genomic analysis. We examined global gene expression in Drosophila melanogaster and report a dramatic underrepresentation of X-chromosome genes showing high relative expression in males. Using comparative genomics, we find that these same X-chromosome genes are exceptionally poorly conserved in the mosquito Anopheles gambiae. These data indicate that the X chromosome is a disfavored location for genes selectively expressed in males. 相似文献
14.
Role of histone H3 lysine 27 methylation in X inactivation 总被引:1,自引:0,他引:1
Plath K Fang J Mlynarczyk-Evans SK Cao R Worringer KA Wang H de la Cruz CC Otte AP Panning B Zhang Y 《Science (New York, N.Y.)》2003,300(5616):131-135
The Polycomb group (PcG) protein Eed is implicated in regulation of imprinted X-chromosome inactivation in extraembryonic cells but not of random X inactivation in embryonic cells. The Drosophila homolog of the Eed-Ezh2 PcG protein complex achieves gene silencing through methylation of histone H3 on lysine 27 (H3-K27), which suggests a role for H3-K27 methylation in imprinted X inactivation. Here we demonstrate that transient recruitment of the Eed-Ezh2 complex to the inactive X chromosome (Xi) occurs during initiation of X inactivation in both extraembryonic and embryonic cells and is accompanied by H3-K27 methylation. Recruitment of the complex and methylation on the Xi depend on Xist RNA but are independent of its silencing function. Together, our results suggest a role for Eed-Ezh2-mediated H3-K27 methylation during initiation of both imprinted and random X inactivation and demonstrate that H3-K27 methylation is not sufficient for silencing of the Xi. 相似文献
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16.
The signal for sex determination in the nematode Caenorhabditis elegans is the ratio of the number of X chromosomes to the number of sets of autosomes (X/A ratio). By previous genetic tests, elements that feminized chromosomal males appeared to be widespread on the X chromosome, but the nature of these elements was not determined. In experiments to define a feminizing element molecularly, cloned sequences were added to chromosomally male embryos by microinjection into the mother. Three different X-chromosome clones, including part of an actin gene, part of a myosin heavy chain gene, and all of two myosin light chain genes, feminize chromosomal males. Both somatic and germline aspects of sex determination are affected. In contrast, about 40 kilobases of nematode autosomal DNA, phage lambda DNA, and plasmid pBR322 DNA do not affect sex determination. A feminizing region was localized to a maximum of 131 base pairs within an intron of the X-linked actin gene; a part of the gene that does not have this region is not feminizing. The results suggest that short, discrete elements found associated with many X-linked genes may act as signals for sex determination in C. elegans. 相似文献
17.
Cloning of human androgen receptor complementary DNA and localization to the X chromosome 总被引:55,自引:0,他引:55
D B Lubahn D R Joseph P M Sullivan H F Willard F S French E M Wilson 《Science (New York, N.Y.)》1988,240(4850):327-330
The androgen receptor (AR) mediates the actions of male sex steroids. Human AR genomic DNA was cloned from a flow-sorted human X chromosome library by using a consensus nucleotide sequence from the DNA-binding domain of the family of nuclear receptors. The AR gene was localized on the human X chromosome between the centromere and q13. Cloned complementary DNA, selected with an AR-specific oligonucleotide probe, was expressed in monkey kidney (COS) cells and yielded a high-affinity androgen-binding protein with steroid-binding specificity corresponding to that of native AR. A predominant messenger RNA species of 9.6 kilobases was identified in human, rat, and mouse tissues known to contain AR and was undetectable in tissues lacking AR androgen-binding activity, including kidney and liver from androgen-insensitive mice. The deduced amino acid sequence of AR within the DNA-binding domain has highest sequence identity with the progesterone receptor. 相似文献
18.
RUSSELL LB 《Science (New York, N.Y.)》1963,140(3570):976-978
In its simplest form the hypothesis of the single-active-X chromosome does not explain variegated-type position effects in the mouse. Inactivity appears not to involve one entire X chromosome; furthermore, even those parts of the chromosome that can change to an inactive state spread inactivation not to the entire attached piece of autosome, but along a gradient to limited distances. 相似文献
19.
Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17 总被引:62,自引:0,他引:62
D Barker E Wright K Nguyen L Cannon P Fain D Goldgar D T Bishop J Carey B Baty J Kivlin 《Science (New York, N.Y.)》1987,236(4805):1100-1102
Linkage analysis of 15 Utah kindreds demonstrated that a gene responsible for von Recklinghausen neurofibromatosis (NF) is located near the centromere on chromosome 17. The families also gave no evidence for heterogeneity, indicating that a significant proportion of NF cases are due to mutations at a single locus. Further genetic analysis can now refine this localization and may lead to the eventual identification and cloning of the defective gene responsible for this disorder. 相似文献
20.
Fragile X genotype characterized by an unstable region of DNA 总被引:71,自引:0,他引:71
S Yu M Pritchard E Kremer M Lynch J Nancarrow E Baker K Holman J C Mulley S T Warren D Schlessinger 《Science (New York, N.Y.)》1991,252(5010):1179-1181
DNA sequences have been located at the fragile X site by in situ hybridization and by the mapping of breakpoints in two somatic cell hybrids that were constructed to break at the fragile site. These hybrids were found to have breakpoints in a common 5-kilobase Eco RI restriction fragment. When this fragment was used as a probe on the chromosomal DNA of normal and fragile X genotype individuals, alterations in the mobility of the sequences detected by the probe were found only in fragile X genotype DNA. These sequences were of an increased size in all fragile X individuals and varied within families, indicating that the region was unstable. This probe provides a means with which to analyze fragile X pedigrees and is a diagnostic reagent for the fragile X genotype. 相似文献