Showing papers on "Dosage compensation published in 2001"
TL;DR: In many sexually dimorphic species, a mechanism is required to ensure equivalent levels of gene expression from the sex chromosomes, and in mammals, such dosage compensation is achieved by X-chromosome inactivation, a process that presents a unique medley of biological puzzles.
Abstract: In many sexually dimorphic species, a mechanism is required to ensure equivalent levels of gene expression from the sex chromosomes. In mammals, such dosage compensation is achieved by X-chromosome inactivation, a process that presents a unique medley of biological puzzles: how to silence one but not the other X chromosome in the same nucleus; how to count the number of X's and keep only one active; how to choose which X chromosome is inactivated; and how to establish this silent state rapidly and efficiently during early development. The key to most of these puzzles lies in a unique locus, the X-inactivation centre and a remarkable RNA — Xist — that it encodes.
647 citations
TL;DR: The gene eed, a member of the mouse Polycomb group (Pc-G) of genes, is required for primary and secondary trophoblast giant cell development in female embryos and it is suggested that this maintenance activity involves hypoacetylation of the inactivated paternal X chromosome in the extra-embryonic tissues.
Abstract: In mammals, dosage compensation of X-linked genes is achieved by the transcriptional silencing of one X chromosome in the female (reviewed in ref. 1). This process, called X inactivation, is usually random in the embryo proper. In marsupials and the extra-embryonic region of the mouse, however, X inactivation is imprinted: the paternal X chromosome is preferentially inactivated whereas the maternal X is always active. Having more than one active X chromosome is deleterious to extra-embryonic development in the mouse2. Here we show that the gene eed (embryonic ectoderm development)3,4, a member of the mouse Polycomb group (Pc-G) of genes, is required for primary and secondary trophoblast giant cell development in female embryos. Results from mice carrying a paternally inherited X-linked green fluorescent protein (GFP) transgene implicate eed in the stable maintenance of imprinted X inactivation in extra-embryonic tissues. Based on the recent finding that the Eed protein interacts with histone deacetylases, we suggest that this maintenance activity involves hypoacetylation of the inactivated paternal X chromosome in the extra-embryonic tissues.
339 citations
TL;DR: Because the majority of dosage-dependent regulators act negatively, this property can account for the up-regulation of genes in monosomics and hemizygous sex chromosomes to achieve dosage compensation.
327 citations
TL;DR: Genetic evidence is provided that Tsix plays a crucial role in maintaining Xist silencing in cis and in regulation of imprinted X-inactivation in the extra-embryonic tissues.
Abstract: 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.
325 citations
TL;DR: Differences in the structure of human and murine genes indicate that human TSIX was truncated during evolution, which could explain the fact that X inactivation is not imprinted in human placenta, and they raise questions about the role of TSIX in random X in activation.
Abstract: X inactivation is the mammalian method for X-chromosome dosage compensation, but some features of this developmental process vary among mammals. Such species variations provide insights into the essential components of the pathway. Tsix encodes a transcript antisense to the murine Xist transcript and is expressed in the mouse embryo only during the initial stages of X inactivation; it has been shown to play a role in imprinted X inactivation in the mouse placenta. We have identified its counterpart within the human X inactivation center (XIC). Human TSIX produces a >30-kb transcript that is expressed only in cells of fetal origin; it is expressed from human XIC transgenes in mouse embryonic stem cells and from human embryoid-body–derived cells, but not from human adult somatic cells. Differences in the structure of human and murine genes indicate that human TSIX was truncated during evolution. These differences could explain the fact that X inactivation is not imprinted in human placenta, and they raise questions about the role of TSIX in random X inactivation.
129 citations
TL;DR: This work shows equivalent expression of at least six of nine Z chromosome genes in male and female chick embryos by using real-time quantitative PCR, implying that the majority of Z-linked genes in the chicken are dosage compensated.
120 citations
TL;DR: The X chromosomes of mammals and fruit flies exhibit unusual properties that have evolved to deal with the different dosages of X-linked genes in males (XY) and females (XX).
Abstract: The X chromosomes of mammals and fruit flies exhibit unusual properties that have evolved to deal with the different dosages of X-linked genes in males (XY) and females (XX). The X chromosome dosage-compensation mechanisms discovered in these species are evolutionarily unrelated, but exhibit surprising parallels in their regulatory strategies. These features include the importance of noncoding RNAs, and epigenetic spreading of chromatin-modifying activities. Sex chromosomes have posed a fascinating puzzle for biologists. The dissimilar organization, gene content, and regulation of the X and Y chromosomes are thought to reflect selective forces acting on original pairs of identical chromosomes (1–3). The result in many organisms is a male-specific Y chromosome that has lost most of its original genetic content, and a difference in dosage of the X chromosome in males (XY) and females (XX).
114 citations
TL;DR: A model for the targeted assembly of the MSL complex, in which initial binding occurs at ∼35 dispersed chromatin entry sites, followed by spreading in cis into flanking regions, is proposed and mapped the recruitment activity to a 217 bp roX1 fragment that shows male‐specific DNase hypersensitivity and can be preferentially cross‐linked in vivo to theMSL complex.
Abstract: In Drosophila , dosage compensation is controlled by the male‐specific lethal (MSL) complex consisting of MSL proteins and roX RNAs. The MSL complex is specifically localized on the male X chromosome to increase its expression ∼2‐fold. We recently proposed a model for the targeted assembly of the MSL complex, in which initial binding occurs at ∼35 dispersed chromatin entry sites, followed by spreading in cis into flanking regions. Here, we analyze one of the chromatin entry sites, the roX1 gene, to determine which sequences are sufficient to recruit the MSL complex. We found association and spreading of the MSL complex from roX1 transgenes in the absence of detectable roX1 RNA synthesis from the transgene. We mapped the recruitment activity to a 217 bp roX1 fragment that shows male‐specific DNase hypersensitivity and can be preferentially cross‐linked in vivo to the MSL complex. When inserted on autosomes, this small roX1 segment is sufficient to produce an ectopic chromatin entry site that can nucleate binding and spreading of the MSL complex hundreds of kilobases into neighboring regions.
104 citations
TL;DR: Nonrandom X inactivation patterns are also associated with selective female survival in male-lethal X- linked dominant disorders or with variable severity of the phenotype in women carrying X-linked dominant mutations.
Abstract: X chromosome inactivation is a process by which the dosage of proteins transcribed from genes on the X chromosome is equalized between males (XY) and females (XX) through the silencing of most genes on one of the two X chromosomes in females. Although the choice of which of the two X's is inactivated is entirely random, not all women have a 50:50 ratio of cells with one or the other X chromosomes active. A number of different mechanisms lead to extremely skewed ratios and this can result in expression of the phenotype of X-linked recessive disorders in females. Nonrandom X inactivation patterns are also associated with selective female survival in male-lethal X-linked dominant disorders or with variable severity of the phenotype in women carrying X-linked dominant mutations. These features are important for the study and gene identification of X-linked disorders and for counseling of affected families.
104 citations
TL;DR: It is suggested that random (in)activation events are common in genes and gene clusters with a low probability of transcription, which generate variability that natural selection has acted on to evolve stable monoallelic expression.
80 citations
01 Jan 2001
TL;DR: The genes located on the amphibian sex chromosomes lead to the conclusion that there is no common ancestral or conserved sex-linkage group, and despite the accumulated evidence that GSD is operating in Anura and Urodela, there is little substantial information about how it functions.
Abstract: In this chapter the different categories of homomorphic and heteromorphic sex chromosomes, types of sex-determining mechanisms, known sex-linked genes, and data about sex-determining genes in the Amphibia have been compiled. Thorough cytogenetic analyses have shown that both XY/XX and ZW/ZZ sex chromosomes exist in the order Anura and Urodela. In some species quite unusual systems of sex determination have evolved (e.g. 0W-females/00-males or the co-existence of XY/XX and ZW/ZZ sex chromosomes within the same species). In the third order of the Amphibia, the Gymnophiona (or Apoda) there is still no information regarding any aspect of sex determination. Whereas most species of Anura and Urodela present undifferentiated, homomorphic sex chromosomes, there is also a considerable number of species in which an increasing structural complexity of the Y and W chromosomes exists. In various cases, the morphological differentiation of the sex chromosomes occurred as a result of quantitative and/or qualitative changes to the repetitive DNA sequences in the constitutive heterochromatin of the Y and W chromosomes. The greater the structural differences between the sex chromosomes, the lesser the extent of pairing in meiosis. No dosage compensation of the sex-linked genes in the somatic cells of the homogametic (XX or ZZ) individuals have been detected. The genes located to date on the amphibian sex chromosomes lead to the conclusion that there is no common ancestral or conserved sex-linkage group. In all amphibians, genetic sex determination (GSD) seems to operate, although environmental factors may influence sex determination and differentiation. Despite the accumulated evidence that GSD is operating in Anura and Urodela, there is little substantial information about how it functions. Although several DNA sequences homologous to the mammalian ZFY, SRY and SOX genes have been detected in the Anura or Urodela, none of these genes is an appropriate candidate to explain sex determination in these vertebrates.
TL;DR: As the authors gain a better understanding of how males and female develop, they will be able to exert greater control over the manipulation of the sex ratio for the offspring of domestic animals.
TL;DR: An X chromosome-specific microarray carrying 2423 cloned cDNA fragments, which represent up to 1317 different X-chromosomal genes is generated and the detection of a male-viable deletion encompassing three genes illustrates the utility of this array for the identification of small unbalanced chromosome rearrangements.
Abstract: Mutant alleles are frequently characterized by low expression levels. Therefore, cDNA array-based gene expression profiling may be a promising strategy for identifying gene defects underlying monogenic disorders. To study the potential of this approach, we have generated an X chromosome-specific microarray carrying 2423 cloned cDNA fragments, which represent up to 1317 different X-chromosomal genes. As a prelude to testing cell lines from patients with X-linked disorders, this array was used as a hybridization probe to compare gene expression profiles in lymphoblastoid cell lines from normal males, females and individuals with supernumerary X chromosomes. Measurable hybridization signals were obtained for more than half of the genes represented on the chip. A total of 53 genes showed elevated expression levels in cells with multiple X chromosomes and many of these were found to escape X-inactivation. Moreover, the detection of a male-viable deletion encompassing three genes illustrates the utility of this array for the identification of small unbalanced chromosome rearrangements.
TL;DR: It is demonstrated that the in vitro and in vivo phenotypes are specifically attributable to the presence of a PGKneo cassette at the targeted locus, and the context of understanding mechanisms of XIST gene regulation in X inactivation is discussed.
Abstract: In this report we demonstrate primary non-random X chromosome inactivation following targeted mutagenesis of a region immediately upstream of XIST promoter P(1). In heterozygous animals there is a preferential inactivation of the targeted X chromosome in 80--90% of cells. The phenotype correlates with inappropriate activation of XIST in a proportion of the mutant XY embryonic stem cells. Strand-specific analysis revealed increased sense transcription initiating upstream of XIST promoter P(1). There was, however, no discernible effect on transcription from the antisense Tsix gene. We demonstrate that the in vitro and in vivo phenotypes are specifically attributable to the presence of a PGKneo cassette at the targeted locus. These findings are discussed in the context of understanding mechanisms of XIST gene regulation in X inactivation.
TL;DR: It is concluded that silencing of autosomal genes by X inactivation can occur without a delay in the replication timing of the surrounding chromatin, supporting the hypothesis that autosomal chromatin lacks certain features present on the X chromosome that are required for the effective spread and/or maintenance of X in activation.
Abstract: We have analysed the spread of X inactivation in an individual with an unbalanced 46,X,der(X)t(X;10)(q26.3;q23.3) karyotype. Despite being trisomic for the region 10q23.3-qter, both the proband and her aunt with the same karyotype presented only with secondary amenorrhoea and lacked any features normally associated with trisomy of distal 10q. Cytogenetic and molecular studies showed that the derivative X;10 chromosome was exclusively inactive. Transcribed polymorphisms were identified in five genes contained within the translocated region of chromosome 10 and were used to perform allele-specific transcription studies. We showed that four of the genes studied are inactive on the derivative chromosome, directly demonstrating the spread of X inactivation over some 30 Mb of autosomal DNA. However, the most distal gene examined remained active, indicating that this spreading was incomplete. In contrast to the gene expression data, replication timing studies showed no spreading of late replication into the translocated portion of 10q. We conclude that silencing of autosomal genes by X inactivation can occur without a delay in the replication timing of the surrounding chromatin. Our findings support the hypothesis that autosomal chromatin lacks certain features present on the X chromosome that are required for the effective spread and/or maintenance of X inactivation.
TL;DR: In this article, it was shown that the separation of the Z and W sex chromosomes did not take place until after the split of major contemporary lineages, in the late Cretaceous.
Abstract: Birds are characterized by female heterogamety; females carry the Z and W sex chromosomes, while males have two copies of the Z chromosome. We suggest here that full differentiation of the Z and W sex chromosomes of birds did not take place until after the split of major contemporary lineages, in the late Cretaceous. The ATP synthase α-subunit gene is now present in one copy each on the nonrecombining part of the W chromosome ( ATP5A1W ) and on the Z chromosome ( ATP5A1Z ). This gene seems to have evolved on several independent occasions, in different lineages, from a state of free recombination into two sex-specific and nonrecombining variants. ATP5A1W and ATP5A1Z are thus more similar within orders, relative to what W (or Z) are between orders. Moreover, this cessation of recombination apparently took place at different times in different lineages (estimated at 13, 40, and 65 million years ago in Ciconiiformes, Galliformes, and Anseriformes, respectively). We argue that these observations are the result of recent and traceable steps in the process where sex chromosomes gradually cease to recombine and become differentiated. Our data demonstrate that this process, once initiated, may occur independently in parallel in sister lineages.
TL;DR: Sex‐linked expression of relative eyespan is likely to be commensurate with the size of the X chromosome in this dramatically dimorphic species, especially if X‐linked genes in males exhibit dosage compensation by twofold hyperactivation, as has been observed in other flies.
Abstract: Recent theoretical and empirical work has suggested that the X chromosome may play a special role in the evolution of sexually dimorphic traits. We tested this idea by quantifying sex chromosome influence on male relative eyespan, a dramatically sexually selected trait in the stalk-eyed fly, Cyrtodiopsis dalmanni. After 31 generations of artificial sexual selection on eyespan:body length ratio, we reciprocally crossed high- with low-line flies and found no evidence for maternal effects; the relative eyespan of F1 females from high- and low-line dams did not differ. However, F1 male progeny from high-line dams had longer relative eyespan than male progeny from low-line dams, indicating X-linkage. Comparison of progeny from a backcross involving reciprocal F1 males and control line females confirmed X-linked inheritance and indicated no effect of the Y chromosome on relative eyespan. We estimated that the X chromosome accounts for 25% (SE 5 6%) of the change in selected lines, using the average difference between reciprocal F1 males divided by the difference between parental males, or 34%, using estimates of the number of effective factors obtained from reciprocal crosses between a high and low line. These estimates exceed the relative size of the X in the diploid genome of a male, 11.9% (SE 5 0.3%), as measured from mitotic chromosome lengths. However, they match expectations if X-linked genes in males exhibit dosage compensation by twofold hyperactivation, as has been observed in other flies. Therefore, sex-linked expression of relative eyespan is likely to be commensurate with the size of the X chromosome in this dramatically dimorphic species.
TL;DR: Applying RNA fluorescence in situ hybridization to parthenogenetic embryos with two maternally derived X (X(M)) chromosomes and embryos with X chromosome aneuploidy and X(P)0, data suggest that imprinted X-inactivation in non-epiblast tissues of rodents had been derived from the random X- inactivation system.
Abstract: Applying RNA fluorescence in situ hybridization to parthenogenetic embryos with two maternally derived X (X(M)) chromosomes and embryos with X chromosome aneuploidy such as X(P)0 (X(P), paternally derived X chromosome), X(M)X(M)X(P) and X(M)X(M)Y, we studied the control of Xist/Tsix expression for silencing the entire X chromosome in mice. The data show that the paternally derived Xist allele is highly expressed in every cell of the embryo from the 4-cell stage onward, irrespective of the number of X chromosomes in a diploid cell. The high level of Xist transcription is maintained in non-epiblast cells culminating in X(P)-inactivation, whereas in X(P)0 embryos it is terminated by the blastocyst stage, probably as a result of counting the number of X chromosomes in a cell occurring at the morula/blastocyst stage. Xist is also down-regulated in epiblast cells of X(M)X(P) and X(M)X(M)X(P) embryos to make X-inactivation random. In epiblast cells, Xist seems to be up-regulated after counting and random choice of the future inactive X chromosome(s). Although the maternal Xist allele is never activated in fertilized embryos before implantation, some parthenogenetic embryos show Xist up-regulation in a proportion of cells. These and other data reported earlier suggest that imprinted X-inactivation in non-epiblast tissues of rodents had been derived from the random X-inactivation system.
01 Jan 2001
TL;DR: In female mammals, all X chromosomes except one are transcriptionally inactivated early in embryonic development, known as X-chromosome inactivation and is a form of dosage compensation, giving equal dosage of the products of X-linked genes in males and females.
Abstract: In female mammals, all X chromosomes except one are transcriptionally inactivated early in embryonic development. This is known as X-chromosome inactivation and is a form of dosage compensation, giving equal dosage of the products of X-linked genes in males and females. The mechanism is of considerable interest as an example of differential behavior of homologous chromatin within the same cell. The system is controlled by the X-inactivation center, a complex locus on the X chromosome, and the key gene is termed Xist. The activity of Xist is controlled by various untranslated RNAs, but polycomb proteins and pluripotency factors play a role at specific stages of embryonic development. At least one gene is thought to be involved in counting X chromosomes and ensuring that a single one remains active in every cell. Some results of recent research are summarized.
TL;DR: This study shows that insertion of either roX1 or roX2 DNA sequences, upstream of an insulated lacZ reporter gene controlled with the constitutive armadillo promoter, results in a significant elevation of expression of lacZ in males.
TL;DR: Two areas of deletion on chromosome 6q were identified in cervical tumors, suggesting the presence of tumor suppressor gene(s) inactivated in this neoplasia.
TL;DR: There is functional disomy of Xp11‐p21.2 in the cells with an active dup(X), most likely resulting in abnormal clinical findings in the patient.
Abstract: We describe a female infant with severe abnormal phenotype with a de novo partial duplication of the short arm of the X chromosome. Chromosome painting confirmed the origin of this X duplication. Molecular cytogenetic analysis with fluorescence in situ hybridization (FISH) was performed with YAC probes, further delineating the breakpoints. The karyotype was 46, X dup(X)(p11-p21.2). Cytogenetic replication studies showed that the normal and duplicated X chromosomes were randomly inactivated in lymphocytes. In most females with structurally abnormal X chromosomes, the abnormal chromosome is inactivated and they are phenotypically apparently normal relatives of phenotypically abnormal males having dupX. Therefore, in this case, there is functional disomy of Xp11-p21.2 in the cells with an active dup(X), most likely resulting in abnormal clinical findings in the patient.
TL;DR: An unusual feature of X inactivation is considered, the mosaic nature of the female and subsequent exposure to somatic cell selection, which brings about equality of expression of most X-linked genes in females and males.
Abstract: The biology of the X chromosome is unique, as there are two Xs in females and only a single X in males, whereas the autosomes are present in duplicate in both sexes. The presence of only a single autosome, which can occur as a result of an error in meiotic segregation, is invariably an embryonic lethal event. Monosomy for the X chromosome is viable because of dosage compensation, a system found in all organisms with an X:Y form of sex determination, which brings about equality of expression of most X-linked genes in females and males. In mammals, the dosage compensation system involves silencing of most of the genes on one X chromosome; it is called X chromosome inactivation. In this review, we focus first on recent advances in our understanding of the molecular basis of the X inactivation mechanism. Then we consider an unusual feature of X inactivation, the mosaic nature of the female and subsequent exposure to somatic cell selection.
01 Jun 2001
TL;DR: The results indicate that the normal allele of the MeCP2 gene could escape X inactivation and reduce the pathogenic effect of mutated allele in RTT, and support the hypothesis proposing the disturbances in dosage compensation effect due to aberrant activation of genes in inactive chromosome X inRTT.
Abstract: Differential replication staining using the 5-bromo-2'-deoxyuridine+Hoechst 33258 technique has been carried out on a series of 28 girls with Rett syndrome (RTT). The results indicated that regions Xq23 and Xq28 of inactive chromosome X could contain early replicating and, therefore, transcriptionally active loci in RTT. Interphase fluorescence in situ hybridization studies of replication timing, using chromosome X-specific genomic DNA probes, was applied to determine the loci with altered replication and transcription in RTT. Randomly selected P1 artificial chromosome (PAC) clones for Xp, Xcen and Xq were used. Two PAC clones from Xq28 (anonymous clone 24.23.0 and 671D9, containing MeCP2 locus) probably escape inactivation in late replicating chromosome X in some RTT patients. Therefore, region Xq28 could contain the genes escaping X inactivation and with expression from the human active and inactive X chromosomes. These results support the hypothesis proposing the disturbances in dosage compensation effect due to aberrant activation of genes in inactive chromosome X in RTT (bi-allelic expression instead of mono-allelic). Our results indicate that the normal allele of the MeCP2 gene could escape X inactivation and reduce the pathogenic effect of mutated allele in RTT.
TL;DR: This issue of PNAS extends studies to address a fundamental question concerning the potential function of Tsix—does its antagonistic relationship to Xist depend on its own noncoding RNA product or does it reflect actions at the DNA level, independent of transcription?
Abstract: The concept of the X inactivation center (Xic) as the master regulatory locus for X inactivation dates back to the mid-1960s (1, 2), not long after X chromosome inactivation itself was proposed as the mammalian dosage compensation mechanism (3–5). Defined genetically as the cis-acting locus required for an X chromosome to undergo inactivation early in female embryogenesis, the Xic defied molecular characterization for nearly 30 years until the discovery of the XIST gene (6), whose noncoding RNA product is transcribed from and remains intimately associated with the inactive X chromosome in female somatic cells (6–9). Xist in both humans and mice maps to the Xic region on the X chromosome and thus became a compelling candidate for a component of the Xic itself (10–12). Biology is rarely as simple as it first appears, however, and X inactivation embodies this principle fully! Only a few years ago, Lee and colleagues (13) described another component of the Xic just downstream of Xist, the Tsix gene, so-named because it consists of an antisense transcript of Xist and whose pattern of expression suggested a potential role as a regulator of Xist. Now, in this issue of PNAS, Stavropoulos et al. (14) extend these studies to address a fundamental question concerning the potential function of Tsix—does its antagonistic relationship to Xist depend on its own noncoding RNA product or does it reflect actions at the DNA level, independent of transcription?
TL;DR: This demonstration of an autoantibody recognizing an antigen(s) associated with the Barr body presents a strategy for identifying molecular components of the BarrBody and examining the molecular basis of X inactivation.
Abstract: Transcriptional inactivation of one X chromosome in mammalian female somatic cells leads to condensation of the inactive X chromosome into the heterochromatic sex chromatin, or Barr body. Little is known about the molecular composition and structure of the Barr body or the mechanisms leading to its formation in female nuclei. Because human sera from patients with autoimmune diseases often contain antibodies against a variety of cellular components, we reasoned that some autoimmune sera may contain antibodies against proteins associated with the Barr body. Therefore, we screened autoimmune sera by immunofluorescence of human fibroblasts and identified one serum that immunostained a distinct nuclear structure with a size and nuclear localization consistent with the Barr body. The number of these structures was consistent with the number of Barr bodies expected in diploid female fibroblasts containing two to five X chromosomes. Immunostaining with the serum followed by fluorescence in situ hybridization with a probe against XIST RNA demonstrated that the major fluorescent signal from the autoantibody colocalized with XIST RNA. Further analysis of the serum showed that it stains human metaphase chromosomes and a nuclear structure consistent with the inactive X in female mouse fibroblasts. However, it does not exhibit localization to a Barr body-like structure in female mouse embryonic stem cells or in cells from female mouse E7.5 embryos. The lack of staining of the inactive X in cells from female E7.5 embryos suggests the antigen(s) may be involved in X inactivation at a stage subsequent to initiation of X inactivation. This demonstration of an autoantibody recognizing an antigen(s) associated with the Barr body presents a strategy for identifying molecular components of the Barr body and examining the molecular basis of X inactivation.
01 Jan 2001
TL;DR: Investment in developing physical and genetic maps of the chicken genome and modern molecular approaches to analyzing gene expression should help to elucidate the sex-determining mechanism in birds in the near future.
Abstract: The morphological development of the embryonic gonads is very similar in birds and mammals, and recent evidence suggests that the genes involved in this process are conserved between these classes of vertebrates. The genetic mechanism by which sex is determined in birds remains to be elucidated, although recent studies have reinforced the contention that steroids may play an important role in the structural development of the testes and ovaries in birds. So far, few genes have been assigned to the avian sex chromosomes, but it is known that the Z and W chromosomes do not share significant homology with the mammalian X and Y chromosomes. The commercial importance of poultry breeding has motivated considerable investment in developing physical and genetic maps of the chicken genome. These efforts, in combination with modern molecular approaches to analyzing gene expression, should help to elucidate the sex-determining mechanism in birds in the near future.
TL;DR: FISH analysis of metaphase chromosomes in a cohort of 33 girls with Rett syndrome allowed us to detect eight girls with structurally different X chromosomes, one X chromosome with a large and another one with a small centromeric heterochromatin (so-called chromosomal heteromorphism).
Abstract: We have developed an approach to differentiate homologous X chromosomes in metaphase chromosomes and interphase nuclei by a fluorescence in situ hybridization (FISH) technique with chromosome X-specific alpha-satellite DNA probe. FISH analysis of metaphase chromosomes in a cohort of 33 girls with Rett syndrome (RTT) allowed us to detect eight girls with structurally different X chromosomes, one X chromosome with a large and another one with a small centromeric heterochromatin (so-called chromosomal heteromorphism). Step-wise application of differential replication staining and the FISH technique to identify the inactivation status of paternal and maternal chromosome X in RTT girls was applied. Skewed X inactivation in seven RTT girls with preferential inactivation of one X chromosome over the other X chromosome was detected in 62-93% of cells. Therefore, non-random or skewed X inactivation with variable penetrance in blood cells could take place in RTT.
TL;DR: In this article the evidence for random inactivation of an X chromosome is reviewed, along with the exceptions that result in nonrandom inactivation.
Abstract: X chromosome inactivation achieves dosage equivalence for most X-linked genes between the two X chromosomes in females and the single X chromosome in males. In this article the evidence for random inactivation of an X chromosome is reviewed, along with the exceptions that result in nonrandom inactivation. Another exception to X chromosome inactivation is the presence of genes that escape inactivation and are expressed from both the active and inactive X chromosomes. The phenotypic consequences of such expression from the inactive X chromosome are discussed. The major players in the process of inactivation are presented. Initiation of inactivation requires the functional RNA, XIST, and the subsequent stable inactivation of the X chromosome relies upon the recruitment of many other factors, the majority of which are generally associated with heterochromatin.