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.

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.

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.

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 Drosophila CLAMP is an essential protein with sex-specific roles in males and females

2016 ◽  
Author(s):  
Jennifer A. Urban ◽  
Caroline A. Doherty ◽  
William T. Jordan ◽  
Jacob E. Bliss ◽  
Jessica Feng ◽  
...  
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Zinc Finger Protein ◽  
Pericentric Heterochromatin ◽  
Single Male ◽  
Essential Protein ◽  
Msl Complex ◽  
Males And Females ◽  
Male Specific

AbstractDosage compensation is a fundamental mechanism in many species that corrects for the inherent imbalance in X-chromosome copy number between XY males and XX females. In Drosophila melanogaster, transcriptional output from the single male X-chromosome is equalized to that of XX females by recruitment of the Male Specific Lethal (MSL) complex to specific sequences along the length of the X-chromosome. The initial recruitment of MSL complex to the X-chromosome is dependent on a recently discovered zinc finger protein called Chromatin-Linked Adapter for MSL Proteins (CLAMP). However, further studies on the in vivo function of CLAMP remained difficult because the location of the gene in pericentric heterochromatin made it challenging to create null mutations or deficiencies. Using the CRISPR/Cas9 genome editing system, we generated the first null mutant in the clamp gene that eliminates expression of CLAMP protein. We show that CLAMP is necessary for both male and female viability. While females die at the third instar larval stage, males die earlier, likely due to the essential role of CLAMP in male dosage compensation. Moreover, we demonstrate that CLAMP promotes dosage compensation in males and represses key male-specific transcripts involved in sex-determination in females. Our results reveal that CLAMP is an essential protein with dual roles in males and females, which together assure that dosage compensation is a sex-specific process.

Dosage Compensation in Drosophila: Evidence That daughterless and Sex-lethal Control X Chromosome Activity at the Blastoderm Stage of Embryogenesis

Genetics ◽  
1987 ◽  
Vol 117 (3) ◽  
pp. 477-485
Author(s):  
J Peter Gergen
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Lethal Gene ◽  
Gene Products ◽  
Lethal Control ◽  
Eye Color ◽  
Phenotypic Assay ◽  
Sex Lethal ◽  
Blastoderm Stage

ABSTRACT Dosage compensation is a mechanism that equalizes the expression of X chromosome linked genes in males, who have one X chromosome, with that in females, who have two. In Drosophila, this is achieved by the relative hyperactivation of X-linked genes in males, as was first shown by Muller using a phenotypic assay based on adult eye color. Several genes involved in regulating dosage compensation have been identified through the isolation of mutations that are sex-specific lethals. However, because of this lethality it is not straightforward to assay the relative roles of these genes using assays based on adult phenotypes. Here this problem is circumvented using an assay based on embryonic phenotypes. These experiments indicate that dosage compensation is established early in development and demonstrate that the daughterless and Sex-lethal gene products are involved in regulating X chromosome activity at the blastoderm stage of embryogenesis.

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.

Dosage Compensation of the X Chromosome: A Complex Epigenetic Assignment Involving Chromatin Regulators and Long Noncoding RNAs

2018 ◽  
Vol 87 (1) ◽  
pp. 323-350 ◽  
Author(s):  
Maria Samata ◽  
Asifa Akhtar
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Transcriptional Activation ◽  
Gene Dosage ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Histone H4 ◽  
Chromosome Conformation ◽  
Msl Complex ◽  
Male Specific

X chromosome regulation represents a prime example of an epigenetic phenomenon where coordinated regulation of a whole chromosome is required. In flies, this is achieved by transcriptional upregulation of X chromosomal genes in males to equalize the gene dosage differences in females. Chromatin-bound proteins and long noncoding RNAs (lncRNAs) constituting a ribonucleoprotein complex known as the male-specific lethal (MSL) complex or the dosage compensation complex mediate this process. MSL complex members decorate the male X chromosome, and their absence leads to male lethality. The male X chromosome is also enriched with histone H4 lysine 16 acetylation (H4K16ac), indicating that the chromatin compaction status of the X chromosome also plays an important role in transcriptional activation. How the X chromosome is specifically targeted and how dosage compensation is mechanistically achieved are central questions for the field. Here, we review recent advances, which reveal a complex interplay among lncRNAs, the chromatin landscape, transcription, and chromosome conformation that fine-tune X chromosome gene expression.

scholarly journals A Plasmid Model System Shows that Drosophila Dosage Compensation Depends on the Global Acetylation of Histone H4 at Lysine 16 and Is Not Affected by Depletion of Common Transcription Elongation Chromatin Marks

2007 ◽  
Vol 27 (22) ◽  
pp. 7865-7870 ◽  
Author(s):  
Ruth Yokoyama ◽  
Antonio Pannuti ◽  
Huiping Ling ◽  
Edwin R. Smith ◽  
John C. Lucchesi
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Regulatory Mechanism ◽  
Model System ◽  
Special Role ◽  
Gene Products ◽  
Histone H4 ◽  
Linked Gene ◽  
Experimental Approaches ◽  
Transcriptional Units

ABSTRACTDosage compensation refers to the equalization of most X-linked gene products between males, which have one X chromosome and a single dose of X-linked genes, and females, which have two X's and two doses of such genes. We developed a plasmid-based model of dosage compensation that allows new experimental approaches for the study of this regulatory mechanism. InDrosophila melanogaster, an enhanced rate of transcription of the X chromosome in males is dependent upon the presence of histone H4 acetylated at lysine 16. This chromatin mark occurs throughout active transcriptional units, leading us to the conclusion that the enhanced level of transcription is achieved through an enhanced rate of RNA polymerase elongation. We used the plasmid model to demonstrate that enhancement in the level of transcription does not depend on other histone marks and factors that have been associated with the process of elongation, thereby highlighting the special role played by histone H4 acetylated at lysine 16 in this process.

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