Male-specific lethal 2, a dosage compensation gene of Drosophila, undergoes sex-specific regulation and encodes a protein with a RING finger and a metallothionein-like cysteine cluster.

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.

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

Cells ◽

10.3390/cells9020323 ◽

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.

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Sex-specific regulation of the male-specific lethal-1 dosage compensation gene in Drosophila.

Genes & Development ◽

10.1101/gad.8.6.698 ◽

1994 ◽

Vol 8 (6) ◽

pp. 698-706 ◽

Cited By ~ 51

Author(s):

M J Palmer ◽

R Richman ◽

L Richter ◽

M I Kuroda

Keyword(s):

Dosage Compensation ◽

Male Specific Lethal ◽

Specific Regulation ◽

Male Specific

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Rapid Evolution of Autosomal Binding Sites of the Dosage Compensation Complex in Drosophila melanogaster and Its Association With Transcription Divergence

Frontiers in Genetics ◽

10.3389/fgene.2021.675027 ◽

2021 ◽

Vol 12 ◽

Author(s):

Aimei Dai ◽

Yushuai Wang ◽

Anthony Greenberg ◽

Zhongqi Liufu ◽

Tian Tang

Keyword(s):

Drosophila Melanogaster ◽

Dosage Compensation ◽

Binding Sites ◽

Protein Sequence ◽

Rapid Evolution ◽

Close Relative ◽

Sequence Evolution ◽

Male Specific Lethal ◽

Msl Complex ◽

Male Specific

How pleiotropy influences evolution of protein sequence remains unclear. The male-specific lethal (MSL) complex in Drosophila mediates dosage compensation by 2-fold upregulation of the X chromosome in males. Nevertheless, several MSL proteins also bind autosomes and likely perform functions not related to dosage compensation. Here, we study the evolution of MOF, MSL1, and MSL2 biding sites in Drosophila melanogaster and its close relative Drosophila simulans. We found pervasive expansion of the MSL binding sites in D. melanogaster, particularly on autosomes. The majority of these newly-bound regions are unlikely to function in dosage compensation and associated with an increase in expression divergence between D. melanogaster and D. simulans. While dosage-compensation related sites show clear signatures of adaptive evolution, these signatures are even more marked among autosomal regions. Our study points to an intriguing avenue of investigation of pleiotropy as a mechanism promoting rapid protein sequence evolution.

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

Genetics ◽

10.1093/genetics/150.2.699 ◽

1998 ◽

Vol 150 (2) ◽

pp. 699-709 ◽

Cited By ~ 3

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.

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

Development ◽

10.1242/dev.122.9.2751 ◽

1996 ◽

Vol 122 (9) ◽

pp. 2751-2760 ◽

Cited By ~ 1

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.

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