scholarly journals Targeting of the dosage-compensated male X-chromosome during early Drosophila development

2019 ◽  
Author(s):  
LE Rieder ◽  
WT Jordan ◽  
EN Larschan
Keyword(s):  
Early Development ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Binding Sites ◽  
Zinc Finger Protein ◽  
Multi Stage ◽  
Compensation Factor ◽  
Zygotic Transcription ◽  
Male Specific ◽  
Lethal Dosage

ABSTRACTThe essential process of dosage compensation, which corrects for the imbalance in X-linked gene expression between XX females and XY males, represents a key model for how genes are targeted for coordinated regulation. However, the mechanism by which dosage compensation complexes identify the X-chromosome during early development remained unknown because of the difficulty of sexing embryos prior to zygotic transcription. We used meiotic drive to sex Drosophila embryos prior to zygotic transcription and ChIP-seq to measure dynamics of dosage compensation factor targeting. The Drosophila Male-Specific Lethal dosage compensation complex (MSLc) requires the ubiquitous zinc-finger protein Chromatin-Linked Adaptor for MSL Proteins (CLAMP) to identify the X-chromosome. We observe a multi-stage process in which MSLc first identifies CLAMP binding sites throughout the genome followed by concentration at the strongest X-linked MSLc sites. We provide insight into the dynamic mechanism by which a large transcription complex identifies its binding sites during early development.

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.

scholarly journals The zinc finger protein CLAMP promotes long-range chromatin interactions that mediate dosage compensation of the Drosophila male X-chromosome

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
William Jordan ◽  
Erica Larschan
Keyword(s):  
Long Range ◽  
Zinc Finger ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Binding Sites ◽  
Zinc Finger Protein ◽  
Dimensional Space ◽  
Three Dimensional ◽  
Active Chromatin ◽  
Finger Protein

Abstract Background Drosophila dosage compensation is an important model system for defining how active chromatin domains are formed. The male-specific lethal dosage compensation complex (MSLc) increases transcript levels of genes along the length of the single male X-chromosome to equalize with that expressed from the two female X-chromosomes. The strongest binding sites for MSLc cluster together in three-dimensional space largely independent of MSLc because clustering occurs in both sexes. CLAMP, a non-sex specific, ubiquitous zinc finger protein, binds synergistically with MSLc to enrich the occupancy of both factors on the male X-chromosome. Results Here, we demonstrate that CLAMP promotes the observed three-dimensional clustering of MSLc binding sites. Moreover, the X-enriched CLAMP protein more strongly promotes longer-range three-dimensional interactions on the X-chromosome than autosomes. Genome-wide, CLAMP promotes three-dimensional interactions between active chromatin regions together with other insulator proteins. Conclusion Overall, we define how long-range interactions which are modulated by a locally enriched ubiquitous transcription factor promote hyper-activation of the X-chromosome to mediate dosage compensation.

scholarly journals Enriched G-quadruplexes on the Drosophila Male X Chromosome Function as Insulators of Dosage Compensation Complex

2019 ◽  
Author(s):  
Sheng-Hu Qian ◽  
Lu Chen ◽  
Zhen-Xia Chen
Keyword(s):  
Y Chromosome ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Binding Sites ◽  
Fine Tuning ◽  
Dosage Compensation Complex ◽  
Evolutionary Trajectory ◽  
Male Specific ◽  
Flanking Regions ◽  
Y Chromosome Degeneration

AbstractThe evolution of sex chromosomes has resulted in half X chromosome dosage in males as females. Dosage compensation, or the two-fold upregulation in males, was thus evolved to balance the gene expression between sexes. However, the step-wise evolutionary trajectory of dosage compensation during Y chromosome degeneration is still unclear. Here, we show that the specific structured elements G-quadruplexes (G4s) are enriched on the X chromosome in Drosophila melanogaster. Meanwhile, on the X chromosome, the G4s are underrepresented on the H4K16 acetylated regions and the binding sites of dosage compensation complex male-specific lethal (MSL) complex. Peaks of G4 density and potential are observed at the flanking regions of MSL binding sites, suggesting G4s act as insulators to precisely up-regulate certain regions in males. Thus, G4s may be involved in the evolution of dosage compensation process through fine-tuning one-dose proto-X chromosome regions around MSL binding sites during the gradual Y chromosome degeneration.One Sentence SummaryG-quadruplexes act as insulators to precisely up-regulate X chromosome in males.

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 Multiple Classes of MSL Binding Sites Target Dosage Compensation to the X Chromosome of Drosophila

2004 ◽  
Vol 14 (6) ◽  
pp. 481-487 ◽  
Author(s):  
Hyangyee Oh ◽  
James R Bone ◽  
Mitzi I Kuroda
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Binding Sites ◽  
Target Dosage

scholarly journals Zinc Finger Protein Zn72D Promotes Productive Splicing of the maleless Transcript

2007 ◽  
Vol 27 (24) ◽  
pp. 8760-8769 ◽  
Author(s):  
Kathleen A. Worringer ◽  
Barbara Panning
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Zinc Finger ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Fluorescent Protein ◽  
Zinc Finger Protein ◽  
General Factor ◽  
Finger Protein ◽  
Msl Complex

ABSTRACT In organisms with sex chromosomes, dosage compensation equalizes gene expression between the sexes. In Drosophila melanogaster males, the male-specific lethal (MSL) complex of proteins and two noncoding roX RNAs coat the X chromosome, resulting in a twofold transcriptional upregulation to equalize gene expression with that of females. How MSL complex enrichment on the X chromosome is regulated is not well understood. We performed an RNA interference screen to identify new factors required for dosage compensation. Using a Drosophila Schneider S2 cell line in which green fluorescent protein (GFP)-tagged MSL2 localizes to the X chromosome, we assayed ∼7,200 knockdowns for their effects on GFP-MSL2 distribution. One factor identified is the zinc finger protein Zn72D. In its absence, the MSL complex no longer coats the X chromosome. We demonstrate that Zn72D is required for productive splicing of the transcript for the MSL protein Maleless, explaining the dosage compensation defect. However, Zn72D is required for the viability of both sexes, indicating its functions are not sex specific. Consistent with this, Zn72D colocalizes with elongating RNA polymerase II, implicating it as a more general factor involved in RNA metabolism.

scholarly journals GA-repeats on mammalian X chromosomes support Ohno’s hypothesis of dosage compensation by transcriptional upregulation

2018 ◽  
Author(s):  
Edridge D’Souza ◽  
Elizaveta Hosage ◽  
Kathryn Weinand ◽  
Steve Gisselbrecht ◽  
Vicky Markstein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transposable Elements ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Binding Sites ◽  
Convergent Evolution ◽  
Fruit Fly ◽  
Dosage Compensation Complex ◽  
X Chromosomes ◽  
Repeat Sequences

ABSTRACTOver 50 years ago, Susumo Ohno proposed that dosage compensation in mammals would require upregulation of gene expression on the single active X chromosome, a mechanism which to date is best understood in the fruit fly Drosophila melanogaster. Here, we report that the GA-repeat sequences that recruit the conserved MSL dosage compensation complex to the Drosophila X chromosome are also enriched across mammalian X chromosomes, providing genomic support for the Ohno hypothesis. We show that mammalian GA-repeats derive in part from transposable elements, suggesting a mechanism whereby unrelated X chromosomes from dipterans to mammals accumulate binding sites for the MSL dosage compensation complex through convergent evolution, driven by their propensity to accumulate transposable elements.

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

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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