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At least 19 recordsLinked to original sources
PubMed1998

SMC proteins and chromosome structure.

The structure of chromosomes is largely determined by chromosome-associated proteins. Members of the SMC (structural maintenance of chromosomes) family play an important role in both prokaryotic and eukaryotic chromosome structure and dynamics. SMC proteins are involved in chromosome condensation, sister-chromatid cohesion, sex-chromosome dosage compensation, genetic recombination and DNA repair. There have been major advances recently in understanding the function of SMC proteins--including the identification of biochemical activities of SMC-containing protein complexes and the realization that individual SMC proteins might link seemingly unrelated aspects of chromosomal metabolism.

Animals↗
PubMed1981

Genetic analysis of the larval secretion gene Sgs-4 and its regulatory chromosome sites in Drosophila melanogaster.

Larval salivary gland secretion from seven wild-type stocks of Drosophila melanogaster was electrophoretically analyzed. Considerable variability occurs in the X-chromosomally coded secretion protein 4, both qualitatively, as expressed by differences in electrophoretic mobilities, and quantitatively as seen by its relative amount in the secretion. Drosophila stocks with "normal" amounts of protein 4 show approximately 80-90% dosage compensation in the males, whereas in two stocks with lower amounts of protein 4 there is no indication of dosage compensation. Genetic analysis showed that the properties of secretion protein 4 and the level of expression of the Sgs-4 gene are controlled by the X-chromosome. Recombination experiments indicate that the stock-specific characteristics of protein 4 are properties of the structural gene Sgs-4 itself or of a chromosome region immediately adjacent to Sgs-4. One recombinant (R+79), manifesting an intermediate level of dosage compensation, indicates that a chromosome segment closely distal to Sg-4 is responsible for the regulation of the gene and for dosage compensation in particular. Accordingly, Sgs-4 must be transcribed from distal to proximal. Its position on the genetic map is 3.6. Two stocks, Hikone-R and Kochi-R, which were originally described as 0-mutants produce very low amounts of a specific secretion protein, 4 h, as revealed by a transvection effect and also by fluorography of overloaded gels.

Animals↗
PubMedDate not supplied

Two doses of the paternal Tme gene do not compensate the lethality of the Thp deletion.

The hairpin-tail (Thp) deletion in chromosome 17 is lethal when it is inherited from the mother, whereas heterozygotes with Thp deletion that is paternal in origin are viable. The lethal effect of maternal Thp is due to a deficiency of the Tme gene that is located in the Thp-deleted region. In this article we describe analysis of the viability of mice with tertiary trisomy of chromosome 17, Ts(17(16]43H, with different doses of the paternal and maternal Tme alleles. We demonstrate that the presence of an additional copy of the region with the Tme gene in the female gamete entirely compensates maternal Thp lethality. We failed to compensate the absence of the Tme gene from the chromosome of maternal derivation by two doses of Tme derived from the father. Thus evidence was obtained indicating that there are significant differences between the activities of the paternal and maternal alleles of the Tme gene due to chromosome imprinting.

Animals↗
PubMed2005

Gene expression analysis of the function of the male-specific lethal complex in Drosophila.

Dosage compensation refers to the equal expression of X-linked genes despite the difference in copy number between the two sexes. The male-specific lethal (MSL) complex is concentrated on the X chromosome in males. A gene expression assay for embryos was developed to examine the function of this complex. In mutant male embryos without either the MSL complex or MOF histone acetylase, dosage compensation is retained but autosomal expression is increased. Dosage compensation is lost in the double-mutant embryos. In embryos in which the MSL complex and MOF are targeted to the X chromosomes in females, the results are consistent with previous surveys showing that in general the X expression remains unchanged, but autosomal expression is reduced. Mutations in the ISWI chromatin-remodeling component cause increases specifically of X-linked genes in males. Thus, the function of the MSL complex in conjunction with ISWI is postulated to override the effect on gene expression of high histone acetylation on the male X. The basic determinant of dosage compensation is suggested to be an inverse dosage effect produced by an imbalance of transcription factors on the X vs. the autosomes. The sequestration of the MSL complex to the male X may have evolved to counteract a similar effect on the autosomes and to prevent an overexpression of the X chromosome in males that would otherwise occur due to the high levels of histone acetylation.

Acetyltransferases↗
PubMed1995

The SMC family: from chromosome condensation to dosage compensation.

Recent genetic analyses in yeasts and biochemical studies in vertebrate cells have led to the discovery of a family of putative ATPases that play a fundamental role in chromosome condensation and segregation in mitosis. One of the members was also found to be involved in dosage compensation in Caenorhabditis elegans, providing a new link between global regulation of gene expression and chromosome structure. This unique family of proteins may control higher-order chromosome dynamics by regulated self-assembly or mechanochemical activity.

Adenosine Triphosphatases↗
PubMed2004

X-inactivation is stably maintained in mouse embryos deficient for histone methyl transferase G9a.

One of the two X chromosomes becomes inactivated during early development of female mammals. Recent studies demonstrate that the inactive X chromosome is rich in histone H3 methylated at Lys-9 and Lys-27, suggesting an important role for these modifications in X-inactivation. It has been shown that in the mouse Eed is required for maintenance of X-inactivation in the extraembryonic lineages. Interestingly, Eed associates with Ezh2 to form a complex possessing histone methyltransferase activity predominantly for H3 Lys-27. We previously showed that G9a is one of the histone methyltransferases specific for H3 Lys-9 and is essential for embryonic development. Here we examined X-inactivation in mouse embryos deficient for G9a. Expression of Xist, which is crucial for the initiation of X-inactivation, was properly regulated and the inactivated X chromosome was stably maintained even in the absence of G9a. These results demonstrate that G9a is not essential for X-inactivation.

Animals↗
PubMed1998

Difference in chromatin packaging between active and inactive X chromosomes by fractionation and allele-specific detection.

Using a novel method consisting of chromatin fractionation and allele-specific detection, chromatin packaging is compared between active X (Xa) and inactive X (Xi) chromosomes for five tumor cell clones that were derived from inter-subspecific F1 female mice. Separation of heterochromatic (H) and euchromatic (E) fractions is monitored by hybridization with subtelomeric satellite DNA and ribosomal RNA gene and by PCR amplification of p53 gene/pseudogene with one primer set. The H fraction was enriched with satellite and p53 pseudogene probably existing in heterochromatic regions while the E fraction showed inverse, suggesting fair separation. Analysis with seven marker and three gene loci revealed concentration of alleles on Xi in the H fraction and those on Xa in the E fraction, though the concentration levels varied. This implies that the packaging level of Xi is higher than that of active or inactive euchromatin on Xa. Intriguingly, one cell line showed biallelic expression and chromatin relaxation of the Pgk-1 locus, suggesting that the relaxation occur regionally on X chromosome.

Alleles↗
PubMed1982

Genetic homology and crossing over in the X and Y chromosomes of Mammals.

The "X-Y crossover model" described in this paper postulates the (1) the pairing observed between the X and the Y chromosome at zygotene is a consequence of genetic homology, (2) there is a single obligatory crossover between the X and Y pacing segments, and (3) the segment of the X which pairs with the Y is protected from subsequent inactivation. Genes distal to the proposed crossover ("pseudoautosomal genes") will appear to be autosomally inherited because they will be transmitted to both male and female offspring. Some criteria for identifying pseudoautosomal genes are outlined. The existence of a single obligatory crossover between the X and Y of the mouse is strongly supported by a recent demonstration that the sex-reversing mutation Sxr, which is passed equally to XX and XY offspring by male carriers, is transmitted on the sex chromosomes. Pseudoautosomally inherited genes may also be responsible for XX sex reversal in goats and familial XX sex reversal in man.

Animals↗
PubMed1997

Coordinate control and variation in X-linked gene expression among female mice.

In normal female mammals, one of the two X Chromosome (Chr) homologs per cell is silenced coordinately during early embryogenesis. The genes located on the inactivated X homolog are predicted to be influenced by the same underlying repression mechanism. To test the uniformity of cis-acting gene repression, 32 genetically identical F1 female mice were analyzed for differential expression of homologous alleles at three X-linked genes-Otc, Atp7a (= Mottled), and Hprt. Gene expression was assayed by the single-nucleotide primer extension (SNuPE) method, thereby allowing the three genes to be quantitated from the same RNA sample. Although variable between individual animals, the relative expression of the two alleles (allelic expression ratio) of the genes is significantly correlated within each steady-state RNA pool. When examined by animal age (3 months to 12 months), no statistically significant differences were observed in the mean or variance of allelic expression ratio. Together, the results confirm that X inactivation is coordinately controlled and is stable across the early- to mid-adult life span.

Adenosine Triphosphatases↗
PubMed1990

Genetic mapping in the region of the mouse X-inactivation center.

The mouse X-inactivation center lies just distal to the T16H breakpoint. Utilizing pedigree analysis of backcross progeny from a Mus domesticus/Mus spretus interspecific cross, we have mapped a number of genetic loci, gene probes, microclones, and EagI linking clones distal to the T16H breakpoint. The genetic analysis provides a detailed genetic map in the vicinity of the mouse X-inactivation center. Comparative mapping data from the human X chromosome indicate that the most probable location of the mouse X-inactivation center is distal to Ccg-1 and in the region of the Pgk-1 locus. We report the assignment of two new loci, EM13 and DXSmh44, to the Ccg-1/Pgk-1 interval.

Animals↗
PubMed2004

Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation.

In many higher organisms, 5%-15% of histone H2A is ubiquitylated at lysine 119 (uH2A). The function of this modification and the factors involved in its establishment, however, are unknown. Here we demonstrate that uH2A occurs on the inactive X chromosome in female mammals and that this correlates with recruitment of Polycomb group (PcG) proteins belonging to Polycomb repressor complex 1 (PRC1). Based on our observations, we tested the role of the PRC1 protein Ring1B and its closely related homolog Ring1A in H2A ubiquitylation. Analysis of Ring1B null embryonic stem (ES) cells revealed extensive depletion of global uH2A levels. On the inactive X chromosome, uH2A was maintained in Ring1A or Ring1B null cells, but not in double knockout cells, demonstrating an overlapping function for these proteins in development. These observations link H2A ubiquitylation, X inactivation, and PRC1 PcG function, suggesting an unanticipated and novel mechanism for chromatin-mediated heritable gene silencing.

Animals↗
PubMedDate not supplied

X inactivation: Tsix and Xist as yin and yang.

A new study shows that expression of Tsix, an antisense Xist gene, can be controlled by imprinting, and that high Tsix activity during X inactivation can protect the future active X chromosome from silencing by Xist. Tsix and Xist seem to have a yin and yang relationship, with opposite effects on X inactivation.

Animals↗
PubMed1993

Parental imprinting on the mouse X chromosome: effects on the early development of X0, XXY and XXX embryos.

To examine the effects of X-chromosome imprinting during early mouse embryogenesis, we attempted to produce XM0, XP0, XMXMY, XMXPY and XMXMXP (where XM and XP stand for the maternally and the paternally derived X chromosome, respectively) making use of mouse strains bearing the translocation Rb(X.2)2Ad and the inversion In(X)1H. Unlike XMXPY embryos, XMXMY and XMXMXP conceptuses suffered from severe growth retardation or abnormal development characterized by deficient extra-embryonic structures at 6.5-7.5 days post coitum (dpc). A cytogenetic study suggested that two XM chromosomes remaining active in certain nonepiblast cells were responsible for the serious developmental abnormality found in these embryos disomic for XM. Although matings involving females heterozygous for Rb(X.2)Ad hinted at the paucity of XP0 embryos relative to those having the complementary karyotype of XMXMXP, further study of embryos from matings between females heterozygous for In(X)1H and Rb2Ad males did not substantiate this observation. Thus, the extensive peri-implantation loss of XP0 embryos shown by Hunt (1991) may be confined to X0 mothers. Taken together, this study failed to reveal a parentally imprinted X-linked gene essential for early mouse embryogenesis other than the one most probably corresponding to the X-chromosome inactivation centre.

Animals↗
PubMed2005

The DNA sequence of the human X chromosome.

The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.

Animals↗
PubMed2002

Homozygous Tsix mutant mice reveal a sex-ratio distortion and revert to random X-inactivation.

Tsix controls X-chromosome inactivation (XCI) by blocking the accumulation of Xist RNA on the future active X chromosome. Deleting Tsix on one X chromosome (X(Delta)X) skews XCI toward the mutated X chromosome in the female soma. Here I have generated homozygous Tsix-null mice (X(Delta)X(Delta)) to test how deleting the second allele affects the choice of XCI. Homozygosity leads to extremely low fertility and reveals two previously unknown non-mendelian patterns of inheritance. First, the sex ratio is skewed against female births so that one daughter is born for every two to three sons. Second, the pattern of XCI unexpectedly returns to random in surviving X(Delta)X(Delta) mice. Thus, with respect to choice, mutation of Tsix yields a phenotypic abnormality in heterozygotes but not homozygotes. To reconcile the paradox of female loss with apparent reversion to random choice, I propose that deleting both Tsix alleles results in chaotic choice and that randomness in X(Delta)X(Delta) survivors reflects a fortuitous selection of distinct X chromosomes as active and inactive.

Animals↗
PubMed1987

Cytogenetic and molecular studies on a recombinant human X chromosome: implications for the spreading of X chromosome inactivation.

A pericentric inversion of a human X chromosome and a recombinant X chromosome [rec(X)] derived from crossing-over within the inversion was identified in a family. The rec(X) had a duplication of the segment Xq26.3----Xqter and a deletion of Xp22.3----Xpter and was interpreted to be Xqter----Xq26.3::Xp22.3----Xqter. To characterize the rec(X) chromosome, dosage blots were done on genomic DNA from carriers of this rearranged X chromosome using a number of X chromosome probes. Results showed that anonymous sequences from the distal end of the long arm to which probes 4D8, Hx120A, DX13, and St14 bind as well as the locus for glucose-6-phosphate dehydrogenase (G6PD) were duplicated on the rec(X). Mouse-human cell hybrids were constructed that retained the rec(X) in the active or inactive state. Analyses of these hybrid clones for markers from the distal short arm of the X chromosome showed that the rec(X) retained the loci for steroid sulfatase (STS) and the cell surface antigen 12E7 (MIC2); but not the pseudoautosomal sequence 113D. These molecular studies confirm that the rec(X) is a duplication-deficiency chromosome as expected. In the inactive state in cell hybrids, STS and MIC2 (which usually escape X chromosome inactivation) were expressed from the rec(X), whereas G6PD was not. Therefore, in the rec(X) X chromosome inactivation has spread through STS and MIC2 leaving these loci unaffected and has inactivated G6PD in the absence of an inactivation center in the q26.3----qter region of the human X chromosome. The mechanism of spreading of inactivation appears to operate in a sequence-specific fashion. Alternatively, STS and MIC2 may have undergone inactivation initially but could not be maintained in an inactive state.

Abnormalities, Multiple↗