Showing papers on "X hyperactivation published in 1994"
TL;DR: It is found that MLE and MSL-1 bind to the X chromosome in an identical pattern and that the pattern of H4Ac16 on the X is largely coincident with that of MLE/MSl-1, suggesting that synthesis or localization of H 4Ac16 is controlled by the dosage compensation regulatory hierarchy.
Abstract: Dosage compensation in Drosophila occurs by an increase in transcription of genes on the X chromosome in males. This elevated expression requires the function of at least four loci, known collectively as the male-specific lethal (msl) genes. The proteins encoded by two of these genes, maleless (mle) and male-specific lethal-1 (msl-1), are found associated with the X chromosome in males, suggesting that they act as positive regulators of dosage compensation. A specific acetylated isoform of histone H4, H4Ac16, is also detected predominantly on the male X chromosome. We have found that MLE and MSL-1 bind to the X chromosome in an identical pattern and that the pattern of H4Ac16 on the X is largely coincident with that of MLE/MSL-1. We fail to detect H4Ac16 on the X chromosome in homozygous msl males, correlating with the lack of dosage compensation in these mutants. Conversely, in Sxl mutants, we detect H4Ac16 on the female X chromosomes, coincident with an inappropriate increase in X chromosome transcription. These data suggest that synthesis or localization of H4Ac16 is controlled by the dosage compensation regulatory hierarchy. Dosage compensation may involve H4Ac16 function, potentially through interaction with the product of the msl genes.
303 citations
TL;DR: In this paper, the authors proposed that DPY-27 implements dosage compensation by condensing the chromatin structure of X in a manner that causes general reduction of X chromosome expression.
255 citations
TL;DR: Models are discussed in which the cis-acting locus deleted by the Dfs functions as a meiotic pairing center that recruits trans-acting factors onto the chromosomes to nucleate assembly of a crossover-competent complex between the X homologs.
Abstract: This study reports the characterization of a cis-acting locus on the Caenorhabditis elegans X chromosome that is crucial for promoting normal levels of crossing over specifically between the X homologs and for ensuring their proper disjunction at meiosis I. The function of this locus is disrupted by the mutation me8, which maps to the extreme left end of the X chromosome within the region previously implicated by studies of X; A translocations and X duplications to contain a meiotic pairing site. Hermaphrodites homozygous for a deletion of the locus (Df/Df) or heterozygous for a deletion and the me8 mutation (me8/Df) exhibit extremely high level of X chromosome nondisjunction at the reductional division; this is correlated with a sharp decrease in crossing over between the X homologs as evidenced both by reductions in genetic map distances and by the presence of achiasmate chromosomes in cytological preparations of oocyte nuclei. Duplications of the wild-type region that are unlinked to the X chromosome cannot complement the recombination and disjunction defects in trans, indicating that this region must be present in cis to the X chromosome to ensure normal levels of crossing over and proper homolog disjunction. me8 homozygotes exhibit an altered distribution of crossovers along the X chromosome that suggests a defect in processivity along the X chromosome of an event that initiates at the chromosome end. Models are discussed in which the cis-acting locus deleted by the Dfs functions as a meiotic pairing center that recruits trans-acting factors onto the chromosomes to nucleate assembly of a crossover-competent complex between the X homologs. This pairing center might function in the process of homolog recognition, or in the initiation of homologous synapsis.
163 citations
TL;DR: It is proposed that the X chromosome component of the sex-determination signal is the dose of a relatively small number of genes.
Abstract: The primary sex-determination signal of Caenorhabditis elegans is the ratio of X chromosomes to sets of autosomes (X/A ratio). This signal coordinately controls both sex determination and X chromosome dosage compensation. To delineate regions of X that contain counted signal elements, we examined the effect on the X/A ratio of changing the dose of specific regions of X, using duplications in XO animals and deficiencies in XX animals. Based on the mutant phenotypes of genes that are controlled by the signal, we expected that increases (in males) or decreases (in hermaphrodites) in the dose of X chromosome elements could cause sex-specific lethality. We isolated duplications and deficiencies of specific X chromosome regions, using strategies that would permit their recovery regardless of whether they affect the signal. We identified a dose-sensitive region at the left end of X that contains X chromosome signal elements. XX hermaphrodites with only one dose of this region have sex determination and dosage compensation defects, and XO males with two doses are more severely affected and die. The hermaphrodite defects are suppressed by a downstream mutation that forces all animals into the XX mode of sex determination and dosage compensation. The male lethality is suppressed by mutations that force all animals into the XO mode of both processes. We were able to subdivide this region into three smaller regions, each of which contains at least one signal element. We propose that the X chromosome component of the sex-determination signal is the dose of a relatively small number of genes.
50 citations
TL;DR: A new cytochrome P450 gene was found within the wap1-prune genetic region of the Drosophila melanogaster X chromosome and has been designated CYP4D2, which encodes a putative cytochrom P450 of subfamily 4D and has a complex exon-intron structure.
Abstract: A new cytochrome P450 gene was found within the wapl-prune genetic region of the Drosophila melanogaster X chromosome. It encodes a putative cytochrome P450 of subfamily 4D and has been designated CYP4D2. CYP4D2 has a complex exon-intron structure. Both the heme-binding motif and a region diagnostic for family 4 are not interrupted by introns. CYP4D2 lies 20 kb proximal to the previously described CYP4D1 gene (Gandhi et al., 1992). In addition to CYP4D1 and CYP4D2, two other DNA fragments homologous to P450 genes are detected within the wapl-prune region.
34 citations
TL;DR: It is shown that in neuroblasts from third instarDrosophila larvae antisera to H4Ac16, MLE and MSL-1 uniquely label the distal, euchromatic region of the male X chromosome through mitosis, suggesting a limited and relatively compact nuclear domain in male cells.
Abstract: In the fruit flyDrosophila, dosage compensation involves several proteins acting in concert to double the transcriptional activity of genes on the single male X chromosome. Three of these proteins, MLE, MSL-1 and histone H4 acetylated at lysine 16 (H4Ac16), have recently been shown to be located almost exclusively on the male X chromosome in interphase (polytene) cells. We show here that in neuroblasts from third instarDrosophila larvae antisera to H4Ac16, MLE and MSL-1 uniquely label the distal, euchromatic region of the male X chromosome through mitosis. The centromere-proximal, heterochromatic region of the male X is not labelled with these antisera, nor are male autosomes or any chromosomes in female cells. That the association of H4Ac16 with the male X chromosome persists, even when the chromosome is maximally compacted and transcriptionally quiescent, argues that this modified histone is an integral component of the dosage compensation pathway. In the nuclei of interphase neuroblasts from male (but never female) larvae, antibodies to H4Ac16 revealed a small, brightly labelled patch against a background of generally weak nuclear staining. In double-labelling experiments, this patch was also labelled, albeit comparatively weakly, with antibodies to MSL-1. These results strongly suggest that the distal, euchromatic region of the X chromosome in male cells occupies a limited and relatively compact nuclear domain.
32 citations
TL;DR: Xist expression per se cannot be a sufficient signal to inactivate an X chromosome and is expressed in cultured cells developmentally arrested prior to X chromosome inactivation, indicating that theXist transcript is not always derived from an inactive X chromosome.
Abstract: TheXist gene resides on the X chromosome and is expressed in female but not male somatic cells. In female cells, only theXist allele on the inactive X chromosome is transcribed. We investigated the expression ofXist in diploid P10 female embryonal carcinoma cells that have two active X chromosomes.Xist RNA was present in these P10 cells. The X chromosomes in P10 cells carry differentXist alleles whose transcripts can be distinguished by restriction digestion of their cDNAs. Both alleles were expressed. Clones of P10 cells that had lost an X chromosome did not expressXist from the remaining allele. ThusXist is expressed in cultured cells developmentally arrested prior to X chromosome inactivation, indicating that theXist transcript is not always derived from an inactive X chromosome. Therefore,Xist expression per se cannot be a sufficient signal to inactivate an X chromosome.
18 citations