scholarly journals Transposon insertions causing constitutive Sex-lethal activity in Drosophila melanogaster affect Sxl sex-specific transcript splicing.

Genetics ◽  
1995 ◽  
Vol 139 (2) ◽  
pp. 631-648
Author(s):  
M Bernstein ◽  
R A Lersch ◽  
L Subrahmanyan ◽  
T W Cline
Keyword(s):  
Drosophila Melanogaster ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Rna Splicing ◽  
Wild Type ◽  
Gain Of Function ◽  
Positive Regulators ◽  
Sex Lethal ◽  
Male Specific ◽  
Transposon Insertions

Abstract Sex-lethal (Sxl) gene products induce female development in Drosophila melanogaster and suppress the transcriptional hyperactivation of X-linked genes responsible for male X-chromosome dosage compensation. Control of Sxl functioning by the dose of X-chromosomes normally ensures that the female-specific functions of this developmental switch gene are only expressed in diplo-X individuals. Although the immediate effect of X-chromosome dose is on Sxl transcription, during most of the life cycle "on" vs. "off" reflects alternative Sxl RNA splicing, with the female (productive) splicing mode maintained by a positive feedback activity of SXL protein on Sxl pre-mRNA splicing. "Male-lethal" (SxlM) gain-of-function alleles subvert Sxl control by X-chromosome dose, allowing female Sxl functions to be expressed independent of the positive regulators upstream of Sxl. As a consequence, SxlM haplo-X animals (chromosomal males) die because of improper dosage compensation, and SxlM chromosomal females survive the otherwise lethal effects of mutations in upstream positive regulators. Five independent spontaneous SxlM alleles were shown previously to be transposon insertions into what was subsequently found to be the region of regulated sex-specific Sxl RNA splicing. We show that these five alleles represent three different mutant types: SxlM1, SxlM3, and SxlM4. SxlM1 is an insertion of a roo element 674 bp downstream of the translation-terminating male-specific exon. SxlM3 is an insertion of a hobo transposon (not 297 as previously reported) into the 3' splice site of the male exon, and SxlM4 is an insertion of a novel transposon into the male-specific exon itself. We show that these three gain-of-function mutants differ considerably in their ability to bypass the sex determination signal, with SxlM4 being the strongest and SxlM1 the weakest. This difference is also reflected in effects of these mutations on sex-specific RNA splicing and on the rate of appearance of SXL protein in male embryos. Transcript analysis of double-mutant male-viable SxlM derivatives in which the SxlM insertion is cis to loss-of-function mutations, combined with other results reported here, indicates that the constitutive character of these SxlM alleles is a consequence of an alteration of the structure of the pre-mRNA that allows some level of female splicing to occur even in the absence of functional SXL protein. Surprisingly, however, most of the constitutive character of SxlM alleles appears to depend on the mutant alleles' responsiveness, perhaps greater than wild-type, to the autoregulatory splicing activity of the wild-type SXL proteins they produce.

The msl-2 dosage compensation gene of Drosophila encodes a putative DNA-binding protein whose expression is sex specifically regulated by Sex-lethal

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3245-3258 ◽  
Author(s):  
G.J. Bashaw ◽  
B.S. Baker
Keyword(s):  
Dna Binding ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Ring Finger ◽  
The Other ◽  
Male Specific Lethal ◽  
Alternatively Spliced ◽  
Sex Lethal ◽  
Specific Regulation ◽  
Male Specific

In Drosophila dosage compensation increases the rate of transcription of the male's X chromosome and depends on four autosomal male-specific lethal genes. We have cloned the msl-2 gene and shown that MSL-2 protein is co-localized with the other three MSL proteins at hundreds of sites along the male polytene X chromosome and that this binding requires the other three MSL proteins. msl-2 encodes a protein with a putative DNA-binding domain: the RING finger. MSL-2 protein is not produced in females and sequences in both the 5′ and 3′ UTRs are important for this sex-specific regulation. Furthermore, msl-2 pre-mRNA is alternatively spliced in a Sex-lethal-dependent fashion in its 5′ UTR.

scholarly journals Differentiation of a male-specific muscle in Drosophila melanogaster does not require the sex-determining genes doublesex or intersex.

Genetics ◽  
1992 ◽  
Vol 132 (1) ◽  
pp. 179-191
Author(s):  
B J Taylor
Keyword(s):  
Drosophila Melanogaster ◽  
Abdominal Segment ◽  
Specific Form ◽  
Null Alleles ◽  
Abdominal Muscles ◽  
Sexually Dimorphic ◽  
Wild Type ◽  
Specific Muscle ◽  
Sex Lethal ◽  
Male Specific

Abstract A pair of muscles span the fifth abdominal segment of male but not female Drosophila melanogaster adults. To establish whether genes involved in the development of other sexually dimorphic tissues controlled the differentiation of sex-specific muscles, flies mutant for five known sex-determining genes were examined for the occurrence of male-specific abdominal muscles. Female flies mutant for alleles of Sex-lethal, defective in sex determination, or null alleles of transformer or transformer-2 are converted into phenotypic males that formed male-specific abdominal muscles. Both male and female flies, when mutant for null alleles of doublesex, develop as nearly identical intersexes in other somatic characteristics. Male doublesex flies produced the male-specific muscles, whereas female doublesex flies lacked them. Female flies, even when they inappropriately expressed the male-specific form of doublesex mRNA, failed to produce the male-specific muscles. Therefore, the wild-type products of the genes Sex-lethal, transformer and transformer-2 act to prevent the differentiation of male-specific muscles in female flies. However, there is no role for the genes doublesex or intersex in either the generation of the male-specific muscles in males or their suppression in females.

scholarly journals Transcription-Coupled Methylation of Histone H3 at Lysine 36 Regulates Dosage Compensation by Enhancing Recruitment of the MSL Complex in Drosophila melanogaster

2008 ◽  
Vol 28 (10) ◽  
pp. 3401-3409 ◽  
Author(s):  
Oliver Bell ◽  
Thomas Conrad ◽  
Jop Kind ◽  
Christiane Wirbelauer ◽  
Asifa Akhtar ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Histone H3 ◽  
The Body ◽  
Histone H4 ◽  
Histone H3 Methylation ◽  
Msl Complex ◽  
Male Specific ◽  
Active Genes

ABSTRACT In Drosophila melanogaster, dosage compensation relies on the targeting of the male-specific lethal (MSL) complex to hundreds of sites along the male X chromosome. Transcription-coupled methylation of histone H3 lysine 36 is enriched toward the 3′ end of active genes, similar to the MSL proteins. Here, we have studied the link between histone H3 methylation and MSL complex targeting using RNA interference and chromatin immunoprecipitation. We show that trimethylation of histone H3 at lysine 36 (H3K36me3) relies on the histone methyltransferase Hypb and is localized promoter distal at dosage-compensated genes, similar to active genes on autosomes. However, H3K36me3 has an X-specific function, as reduction specifically decreases acetylation of histone H4 lysine 16 on the male X chromosome. This hypoacetylation is caused by compromised MSL binding and results in a failure to increase expression twofold. Thus, H3K36me3 marks the body of all active genes yet is utilized in a chromosome-specific manner to enhance histone acetylation at sites of dosage compensation.

scholarly journals Differential effects of Sex-lethal mutations on dosage compensation early in Drosophila development.

Genetics ◽  
1994 ◽  
Vol 136 (3) ◽  
pp. 1051-1061
Author(s):  
M Bernstein ◽  
T W Cline
Keyword(s):  
Sex Determination ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Rna Splicing ◽  
Lethal Gene ◽  
Loss Of Function ◽  
Developmental Pathway ◽  
Pathway Choice ◽  
Sex Lethal ◽  
Blastoderm Stage

Abstract In response to the primary sex determination signal, X chromosome dose, the Sex-lethal gene controls all aspects of somatic sex determination and differentiation, including X chromosome dosage compensation. Two complementary classes of mutations have been identified that differentially affect Sxl somatic functions: (1) those impairing the "early" function used to set developmental pathway choice in response to the sex determination signal and (2) those impairing "late" functions involved in maintaining the pathway choice independent of the initiating signal and/or in directing differentiation. This "early vs. late" distinction correlates with a switch in promoter utilization from SxlPe to SxlPm at the blastoderm stage and a corresponding switch from transcriptional to RNA splicing control. Here we characterize five partial-loss-of-function Sxl alleles to explore a distinction between "early vs. late" functioning of Sxl in dosage compensation. Assaying for dosage compensation during the blastoderm stage, we find that the earliest phase of the dosage compensation process is controlled by products of the early Sxl promoter, SxlPe. Hence, in addition to triggering the sexual pathway decision of cells, products derived from SxlPe also control early dosage compensation, the first manifestation of sexually dimorphic differentiation. The effects of mutant Sxl alleles on early dosage compensation are consistent with their previous categorization as early vs. late defective with respect to their effects on pathway initiation. Results reported here suggest that the dosage compensation regulatory genes currently known to function downstream of Sxl, genes known as the "male-specific lethals," do not control all aspects of dosage compensation either at the blastoderm stage or later in development. In the course of this study, we also discovered that the canonical early defective allele, Sxlf9, which is impaired in its ability to establish the female developmental pathway commitment, is likely to be defective in the stability and/or functioning of products derived from SxlPe, rather than in the ability of SxlPe to respond to the chromosomal sex determination signal.

scholarly journals Does postzygotic isolation result from improper dosage compensation?

Genetics ◽  
1989 ◽  
Vol 122 (4) ◽  
pp. 891-894
Author(s):  
H A Orr
Keyword(s):  
Drosophila Melanogaster ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Animal Species ◽  
Drosophila Simulans ◽  
Postzygotic Isolation ◽  
Counting System ◽  
Sex Lethal

Abstract The X chromosome invariably has the largest effect on postzygotic isolation between animal species. One explanation of this pattern is that inviability and sterility result from a breakdown in the dosage compensation of X-linked genes in hybrids. In Drosophila, such breakdown could result from divergence of the genes used to assess the X/autosomal (X/A) ratio, and thus the sex, of an individual. I test this hypothesis by introducing mutant alleles of the Sex-lethal locus into Drosophila melanogaster-Drosophila simulans hybrids. These mutants "ignore" any perceived anomalous X/A ratio and thus can be used to ensure proper dosage compensation in hybrids. These mutants do not rescue hybrid viability or fertility, implying that postzygotic isolation in this hybridization does not result from a disruption of dosage compensation caused by divergence of the X/A counting system.

scholarly journals Absence of X-chromosome dosage compensation in the primordial germ cells of Drosophila embryos

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryoma Ota ◽  
Makoto Hayashi ◽  
Shumpei Morita ◽  
Hiroki Miura ◽  
Satoru Kobayashi
Keyword(s):  
X Chromosome ◽  
Germ Cells ◽  
Dosage Compensation ◽  
Sex Chromosome ◽  
Primordial Germ Cells ◽  
Histone H4 ◽  
X Chromosomes ◽  
Essential Components ◽  
Msl Complex ◽  
Male Specific

AbstractDosage compensation is a mechanism that equalizes sex chromosome gene expression between the sexes. In Drosophila, individuals with two X chromosomes (XX) become female, whereas males have one X chromosome (XY). In males, dosage compensation of the X chromosome in the soma is achieved by five proteins and two non-coding RNAs, which assemble into the male-specific lethal (MSL) complex to upregulate X-linked genes twofold. By contrast, it remains unclear whether dosage compensation occurs in the germline. To address this issue, we performed transcriptome analysis of male and female primordial germ cells (PGCs). We found that the expression levels of X-linked genes were approximately twofold higher in female PGCs than in male PGCs. Acetylation of lysine residue 16 on histone H4 (H4K16ac), which is catalyzed by the MSL complex, was undetectable in these cells. In male PGCs, hyperactivation of X-linked genes and H4K16ac were induced by overexpression of the essential components of the MSL complex, which were expressed at very low levels in PGCs. Together, these findings indicate that failure of MSL complex formation results in the absence of X-chromosome dosage compensation in male PGCs.

Sex determination in the germ line of Drosophila melanogaster: activation of the gene Sex-lethal

Development ◽  
1993 ◽  
Vol 118 (3) ◽  
pp. 813-816 ◽  
Author(s):  
B. Granadino ◽  
P. Santamaria ◽  
L. Sanchez
Keyword(s):  
Drosophila Melanogaster ◽  
Germ Cells ◽  
Germ Line ◽  
Wild Type ◽  
Female Development ◽  
Pole Cell ◽  
Somatic Tissues ◽  
Wild Type Female ◽  
Sex Lethal ◽  
Pole Cell Transplantation

The germ line exhibits sexual dimorphism as do the somatic tissues. Cells with the 2X;2A chromosome constitution will follow the oogenic pathway and X;2A cells will develop into sperm. In both somatic and germ-line tissues, the sexual pathway chosen by the cells depends on the gene Sex-lethal (Sxl), whose function is continuously needed for female development. In the soma, the sex of the cells is autonomously determined by the X:A signal while, in the germ line, the sex is determined by cell autonomous (the X:A signal) and somatic inductive signals. Three X-linked genes have been identified, scute (sc), sisterless-a (sis-a) and runt (run), that determine the initial functional state of Sxl in the soma. Using pole cell transplantation, we have tested whether these genes are also needed to activate Sxl in the germ line. We found that germ cells simultaneously heterozygous for sc, sis-a, run and a deficiency for Sxl transplanted into wild-type female hosts develop into functional oocytes. We conclude that the genes sc, sis-a and run needed to activate Sxl in the soma seem not to be required to activate this gene in the germ line; therefore, the X:A signal would be made up by different genes in somatic and germ-line tissues. The Sxlf7M1/Sxlfc females do not have developed ovaries. We have shown that germ cells of this genotype transplanted into wild-type female hosts produce functional oocytes. We conclude that the somatic component of the gonads in Sxlf7M1/Sxlfc females is affected, and consequently germ cells do not develop.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative Genetics of Drosophila Melanogaster. II. Heritabilities and Genetic Correlations between Sexes for Head and Thorax Traits.

Genetics ◽  
1988 ◽  
Vol 119 (2) ◽  
pp. 421-433
Author(s):  
D E Cowley ◽  
W R Atchley
Keyword(s):  
Drosophila Melanogaster ◽  
Sexual Dimorphism ◽  
Genetic Analysis ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Imaginal Disc ◽  
Genetic Correlations ◽  
Body Parts ◽  
Quantitative Genetic ◽  
Males And Females

Abstract A quantitative genetic analysis is reported for traits on the head and thorax of adult fruit flies, Drosophila melanogaster. Females are larger than males, and the magnitude of sexual dimorphism is similar for traits derived from the same imaginal disc, but the level of sexual dimorphism varies widely across discs. The greatest difference between males and females occurs for the dimensions of the sclerotized mouthparts of the proboscis. Most of the traits studied are highly heritable with heritabilities ranging from 0.26 to 0.84 for males and 0.27 to 0.81 for females. In general, heritabilities are slightly higher for males, possibly reflecting the effect of dosage compensation on X-linked variance. The X chromosome contributes substantially to variance for many of these traits, and including results reported elsewhere, the variance for over two-thirds of the traits studied includes X-linked variance. The genetic correlations between sexes for the same trait are generally high and close to unity. Coupled with the small differences in the traits between sexes for heritabilities and phenotypic variances, these results suggest that selection would be very slow to change the level of sexual dimorphism in size of various body parts.

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