scholarly journals The male-specific lethal-one (msl-1) gene of Drosophila melanogaster encodes a novel protein that associates with the X chromosome in males.

Genetics ◽  
1993 ◽  
Vol 134 (2) ◽  
pp. 545-557 ◽  
Author(s):  
M J Palmer ◽  
V A Mergner ◽  
R Richman ◽  
J E Manning ◽  
M I Kuroda ◽  
...  
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Current Data ◽  
Direct Role ◽  
Significant Similarity ◽  
Linked Gene ◽  
Male Specific Lethal ◽  
Male Specific ◽  
Chromatin Modeling ◽  
Novel Protein

Abstract Male-specific lethal-one (msl-1) is one of four genes that are required for dosage compensation in Drosophila males. To determine the molecular basis of msl-1 regulation of dosage compensation, we have cloned the gene and characterized its products. The predicted msl-1 protein (MSL-1) has no significant similarity to proteins in the current data bases but contains an acidic N terminus characteristic of proteins involved in transcription and chromatin modeling. We present evidence that the msl-1 protein is associated with hundreds of sites along the length of the X chromosome in male, but not in female, nuclei. Our findings support the hypothesis that msl-1 plays a direct role in increasing the level of X-linked gene transcription in male nuclei.

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.

Drosophila Male-Specific Lethal 2 Protein Controls Sex-Specific Expression of the roX Genes

Genetics ◽  
2004 ◽  
Vol 166 (4) ◽  
pp. 1825-1832 ◽  
Author(s):  
Barbara P Rattner ◽  
Victoria H Meller
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
X Chromosome ◽  
Specific Expression ◽  
Linked Gene ◽  
Male And Female ◽  
Male Specific Lethal ◽  
Msl Complex ◽  
Male Specific ◽  
Rox Rna

Abstract The MSL complex of Drosophila upregulates transcription of the male X chromosome, equalizing male and female X-linked gene expression. Five male-specific lethal proteins and at least one of the two noncoding roX RNAs are essential for this process. The roX RNAs are required for the localization of MSL complexes to the X chromosome. Although the mechanisms directing targeting remain speculative, the ratio of MSL protein to roX RNA influences localization of the complex. We examine the transcriptional regulation of the roX genes and show that MSL2 controls male-specific roX expression in the absence of any other MSL protein. We propose that this mechanism maintains a stable MSL/roX ratio that is favorable for localization of the complex to the X chromosome.

scholarly journals Painting of Fourth and the X-Linked 1.688 Satellite in D. melanogaster Is Involved in Chromosome-Wide Gene Regulation

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 323
Author(s):  
Samaneh Ekhteraei-Tousi ◽  
Jacob Lewerentz ◽  
Jan Larsson
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Rapid Evolution ◽  
Regulatory Mechanisms ◽  
Expression Of Genes ◽  
Male Specific Lethal ◽  
Msl Complex ◽  
Specific Regulation ◽  
Male Specific ◽  
Genomic Regions

Chromosome-specific regulatory mechanisms provide a model to understand the coordinated regulation of genes on entire chromosomes or on larger genomic regions. In fruit flies, two chromosome-wide systems have been characterized: The male-specific lethal (MSL) complex, which mediates dosage compensation and primarily acts on the male X-chromosome, and Painting of fourth (POF), which governs chromosome-specific regulation of genes located on the 4th chromosome. How targeting of one specific chromosome evolves is still not understood; but repeated sequences, in forms of satellites and transposable elements, are thought to facilitate the evolution of chromosome-specific targeting. The highly repetitive 1.688 satellite has been functionally connected to both these systems. Considering the rapid evolution and the necessarily constant adaptation of regulatory mechanisms, such as dosage compensation, we hypothesised that POF and/or 1.688 may still show traces of dosage-compensation functions. Here, we test this hypothesis by transcriptome analysis. We show that loss of Pof decreases not only chromosome 4 expression but also reduces the X-chromosome expression in males. The 1.688 repeat deletion, Zhr1 (Zygotic hybrid rescue), does not affect male dosage compensation detectably; however, Zhr1 in females causes a stimulatory effect on X-linked genes with a strong binding affinity to the MSL complex (genes close to high-affinity sites). Lack of pericentromeric 1.688 also affected 1.688 expression in trans and was linked to the differential expression of genes involved in eggshell formation. We discuss our results with reference to the connections between POF, the 1.688 satellite and dosage compensation, and the role of the 1.688 satellite in hybrid lethality.

scholarly journals Modulation of MSL1 Abundance in Female Drosophila Contributes to the Sex Specificity of Dosage Compensation

Genetics ◽  
1998 ◽  
Vol 150 (2) ◽  
pp. 699-709 ◽  
Author(s):  
Kimberly A Chang ◽  
Mitzi I Kuroda
Keyword(s):  
Dosage Compensation ◽  
Ectopic Expression ◽  
Negative Regulation ◽  
Limiting Factor ◽  
Control Mechanisms ◽  
Linked Gene ◽  
Male Specific Lethal ◽  
Sex Specificity ◽  
Female Specific ◽  
Male Specific

Abstract Dosage compensation in Drosophila is the mechanism by which X-linked gene expression is made equal in males and females. Proper regulation of this process is critical to the survival of both sexes. Males must turn the male-specific lethal (msl)-mediated pathway of dosage compensation on and females must keep it off. The msl2 gene is the primary target of negative regulation in females. Preventing production of MSL2 protein is sufficient to prevent dosage compensation; however, ectopic expression of MSL2 protein in females is not sufficient to induce an insurmountable level of dosage compensation, suggesting that an additional component is limiting in females. A candidate for this limiting factor is MSL1, because the amount of MSL1 protein in females is reduced compared to males. We have identified two levels of negative regulation of msl1 in females. The predominant regulation is at the level of protein stability, while a second regulatory mechanism functions at the level of protein synthesis. Overcoming these control mechanisms by overexpressing both MSL1 and MSL2 in females results in 100% female-specific lethality.

Evidence that MSL-mediated dosage compensation in Drosophila begins at blastoderm

Development ◽  
1996 ◽  
Vol 122 (9) ◽  
pp. 2751-2760 ◽  
Author(s):  
A. Franke ◽  
A. Dernburg ◽  
G.J. Bashaw ◽  
B.S. Baker
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Dependent Manner ◽  
Gene Products ◽  
Histone H4 ◽  
Single Male ◽  
Somatic Tissues ◽  
Male Specific Lethal ◽  
Male Specific ◽  
Blastoderm Stage

In Drosophila equalization of the amounts of gene products produced by X-linked genes in the two sexes is achieved by hypertranscription of the single male X chromosome. This process, dosage compensation, is controlled by a set of male-specific lethal (msl) genes, that appear to act at the level of chromatin structure. The properties of the MSL proteins have been extensively studied in the polytene salivary gland chromosomes where they bind to the same set of sites along the male X chromosome in a co-dependent manner. Here we report experiments that show that the MSL proteins first associate with the male X chromosome as early as blastoderm stage, slightly earlier than the histone H4 isoform acetylated at lysine 16 is detected on the X chromosome. MSL binding to the male X chromosome is observed in all somatic tissues of embryos and larvae. Binding of the MSLs to the X chromosome is also interdependent in male embryos and prevented in female embryos by the expression of Sex-lethal (Sxl). A delayed onset of binding of the MSLs in male progeny of homozygous mutant msl-1 or mle mothers coupled with the previous finding that such males have an earlier lethal phase supports the idea that msl-mediated dosage compensation begins early in embryogenesis. Other results show that the maleless (MLE) protein on embryo and larval chromosomes differs in its reactivity with antibodies; the functional significance of this finding remains to be explored.

scholarly journals CLAMP directly interacts with MSL2 to facilitate Drosophila dosage compensation

2018 ◽  
Author(s):  
Evgeniya Tikhonova ◽  
Anna Fedotova ◽  
Artem Bonchuk ◽  
Vladic Mogila ◽  
Erica N. Larschan ◽  
...  
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Protein Complexes ◽  
Dna Binding Protein ◽  
Zinc Finger Domain ◽  
Dosage Compensation Complex ◽  
Dna Interactions ◽  
Male Specific Lethal ◽  
Msl Complex ◽  
Male Specific

AbstractThe binding of Drosophila male-specific lethal (MSL) dosage compensation complex exclusively to male X chromosome provides an excellent model system to understand mechanisms of selective recruitment of protein complexes to chromatin. Previous studies showed that the male-specific organizer of the complex, MSL2, and ubiquitous DNA-binding protein CLAMP are key players in the specificity of X chromosome binding. The CXC domain of MSL2 binds to genomic sites of MSL complex recruitment. Here we demonstrated that MSL2 directly interacts with the N-terminal zinc-finger domain of CLAMP. CLAMP-MSL2 and CXC-DNA interactions are cooperatively involved in recruitment of MSL complex to the X chromosome.

scholarly journals Drosophila Dosage Compensation Loci Associate with a Boundary-Forming Insulator Complex

2017 ◽  
Vol 37 (21) ◽  
Author(s):  
Emily G. Kaye ◽  
Amina Kurbidaeva ◽  
Daniel Wolle ◽  
Tsutomu Aoki ◽  
Paul Schedl ◽  
...  
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Boundary Complex ◽  
Bithorax Complex ◽  
Male Specific Lethal ◽  
Topologically Associated Domains ◽  
Complex Boundary ◽  
Recognition Elements ◽  
Male Specific

ABSTRACT Chromatin entry sites (CES) are 100- to 1,500-bp elements that recruit male-specific lethal (MSL) complexes to the X chromosome to upregulate expression of X-linked genes in male flies. CES contain one or more ∼20-bp GA-rich sequences called MSL recognition elements (MREs) that are critical for dosage compensation. Recent studies indicate that CES also correspond to boundaries of X-chromosomal topologically associated domains (TADs). Here, we show that an ∼1,000-kDa complex called the late boundary complex (LBC), which is required for the functioning of the Bithorax complex boundary Fab-7, interacts specifically with a special class of CES that contain multiple MREs. Mutations in the MRE sequences of three of these CES that disrupt function in vivo abrogate interactions with the LBC. Moreover, reducing the levels of two LBC components compromises MSL recruitment. Finally, we show that several of the CES that are physically linked to each other in vivo are LBC interactors.

Dosage Compensation Regulatory Proteins and the Evolution of Sex Chromosomes in Drosophila

Genetics ◽  
1996 ◽  
Vol 144 (2) ◽  
pp. 705-713 ◽  
Author(s):  
James R Bone ◽  
Mitzi I Kuroda
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Sex Chromosome ◽  
Regulatory Proteins ◽  
Histone H4 ◽  
Cis Acting ◽  
Male Specific Lethal ◽  
Chromosome Arm ◽  
Male Specific ◽  
Regulatory Sites

Abstract In the fruitfly Drosophila melanogaster, the four male-specific lethal (msl) genes are required to achieve dosage compensation of the male X chromosome. The MSL proteins are thought to interact with cis-acting sites that confer dosage compensation to nearby genes, as they are detected at hundreds of discrete sites along the length of the polytene X chromosome in males but not in females. The histone H4 acetylated isoform, H4Ac16, colocalizes with the MSL proteins at a majority of sites on the D. melanogaster X chromosome. Using polytene chromosome immunostaining of other species from the genus Drosophila, we found that X chromosome association of MSL proteins and H4Ac16 is conserved despite differences in the sex chromosome karyotype between species. Our results support a model in which cis-acting regulatory sites for dosage compensation evolve on a neo-X chromosome arm in response to the degeneration of its former homologue.

Molecular characterization of the male-specific lethal-3 gene and investigations of the regulation of dosage compensation in Drosophila

Development ◽  
1995 ◽  
Vol 121 (2) ◽  
pp. 463-475 ◽  
Author(s):  
M. Gorman ◽  
A. Franke ◽  
B.S. Baker
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
The Other ◽  
Single Male ◽  
X Chromosomes ◽  
Male Specific Lethal ◽  
Male Specific ◽  
Chromosome Binding

In Drosophila, dosage compensation occurs by transcribing the single male X chromosome at twice the rate of each of the two female X chromosomes. This hypertranscription requires four autosomal male-specific lethal (msl) genes and is negatively regulated by the Sxl gene in females. Two of the msls, the mle and msl-1 genes, encode proteins that are associated with hundreds of specific sites along the length of the male X chromosome. MLE and MSL-1 X chromosome binding are negatively regulated by Sxl in females and require the functions of the other msls in males. To investigate further the regulation of dosage compensation and the role of the msls in this process, we have cloned and molecularly characterized another msl, the msl-3 gene. We have found that MSL-3 is also associated with the male X chromosome. We have further investigated whether Sxl negatively regulates MSL-3 X-chromosome binding in females and whether MSL-3 X-chromosome binding requires the other msls. Our results suggest that the MLE, MSL-1 and MSL-3 proteins may associate with one another in a male-specific heteromeric complex on the X chromosome to achieve its hypertranscription.

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