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.

scholarly journals The Drosophila MSL Complex Acetylates Histone H4 at Lysine 16, a Chromatin Modification Linked to Dosage Compensation

2000 ◽  
Vol 20 (1) ◽  
pp. 312-318 ◽  
Author(s):  
Edwin R. Smith ◽  
Antonio Pannuti ◽  
Weigang Gu ◽  
Arnd Steurnagel ◽  
Richard G. Cook ◽  
...  
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Chromatin Modification ◽  
Gene Products ◽  
Histone H4 ◽  
Linked Gene ◽  
Rna Transcripts ◽  
Msl Complex ◽  
Males And Females

ABSTRACT In Drosophila, dosage compensation—the equalization of most X-linked gene products in males and females—is achieved by a twofold enhancement of the level of transcription of the X chromosome in males relative to each X chromosome in females. A complex consisting of at least five gene products preferentially binds the X chromosome at numerous sites in males and results in a significant increase in the presence of a specific histone isoform, histone 4 acetylated at lysine 16. Recently, RNA transcripts (roX1 and roX2) encoded by two different genes have also been found associated with the X chromosome in males. We have partially purified a complex containing MSL1, -2, and -3, MOF, MLE, and roX2 RNA and demonstrated that it exclusively acetylates H4 at lysine 16 on nucleosomal substrates. These results demonstrate that the MSL complex is responsible for the specific chromatin modification characteristic of the X chromosome in Drosophila males.

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 Two Classes of Dosage Compensation Complex Binding Elements along Caenorhabditis elegans X Chromosomes

2009 ◽  
Vol 29 (8) ◽  
pp. 2023-2031 ◽  
Author(s):  
Timothy A. Blauwkamp ◽  
Gyorgyi Csankovszki
Keyword(s):  
Caenorhabditis Elegans ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Gene Products ◽  
Dosage Compensation Complex ◽  
X Chromosomes ◽  
Linked Gene ◽  
Unknown Mechanism

ABSTRACT Dosage compensation equalizes X-linked gene products between the sexes. In Caenorhabditis elegans, the dosage compensation complex (DCC) binds both X chromosomes in XX animals and halves the transcription from each. The DCC is recruited to the X chromosomes by a number of loci, rex sites, and is thought to spread from these sites by an unknown mechanism to cover the rest of the chromosome. Here we describe a novel class of DCC-binding elements that we propose serve as “way stations” for DCC binding and spreading. Both rex sites and way stations comprise strong foci of DCC binding on the native X chromosome. However, rex sites maintain their ability to bind large amounts of DCC even on X duplications detached from the native X, while way stations do not. These results suggest that two distinct classes of DCC-binding elements facilitate recruitment and spreading of the DCC along the X chromosome.

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.

scholarly journals Finding a Balance: How Diverse Dosage Compensation Strategies Modify Histone H4 to Regulate Transcription

2012 ◽  
Vol 2012 ◽  
pp. 1-12
Author(s):  
Michael B. Wells ◽  
Györgyi Csankovszki ◽  
Laura M. Custer
Keyword(s):  
Gene Expression ◽  
Dosage Compensation ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Current Understanding ◽  
Histone H4 ◽  
Linked Gene ◽  
Expression Levels ◽  
Gene Expression Levels

Dosage compensation balances gene expression levels between the sex chromosomes and autosomes and sex-chromosome-linked gene expression levels between the sexes. Different dosage compensation strategies evolved in different lineages, but all involve changes in chromatin. This paper discusses our current understanding of how modifications of the histone H4 tail, particularly changes in levels of H4 lysine 16 acetylation and H4 lysine 20 methylation, can be used in different contexts to either modulate gene expression levels twofold or to completely inhibit transcription.

scholarly journals Distinct mechanisms mediate X chromosome dosage compensation in Anopheles and Drosophila

2021 ◽  
Vol 4 (9) ◽  
pp. e202000996
Author(s):  
Claudia Isabelle Keller Valsecchi ◽  
Eric Marois ◽  
M Felicia Basilicata ◽  
Plamen Georgiev ◽  
Asifa Akhtar
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Gene Dosage ◽  
Histone H4 ◽  
Ecological Constraints ◽  
Evolutionary Trajectory ◽  
X Chromosomes ◽  
Deleterious Gene ◽  
Msl Complex ◽  
High Degree

Sex chromosomes induce potentially deleterious gene expression imbalances that are frequently corrected by dosage compensation (DC). Three distinct molecular strategies to achieve DC have been previously described in nematodes, fruit flies, and mammals. Is this a consequence of distinct genomes, functional or ecological constraints, or random initial commitment to an evolutionary trajectory? Here, we study DC in the malaria mosquito Anopheles gambiae. The Anopheles and Drosophila X chromosomes evolved independently but share a high degree of homology. We find that Anopheles achieves DC by a mechanism distinct from the Drosophila MSL complex–histone H4 lysine 16 acetylation pathway. CRISPR knockout of Anopheles msl-2 leads to embryonic lethality in both sexes. Transcriptome analyses indicate that this phenotype is not a consequence of defective X chromosome DC. By immunofluorescence and ChIP, H4K16ac does not preferentially enrich on the male X. Instead, the mosquito MSL pathway regulates conserved developmental genes. We conclude that a novel mechanism confers X chromosome up-regulation in Anopheles. Our findings highlight the pluralism of gene-dosage buffering mechanisms even under similar genomic and functional constraints.

scholarly journals The Caenorhabditis elegans gene sdc-2 controls sex determination and dosage compensation in XX animals.

Genetics ◽  
1989 ◽  
Vol 122 (3) ◽  
pp. 579-593 ◽  
Author(s):  
C Nusbaum ◽  
B J Meyer
Keyword(s):  
Caenorhabditis Elegans ◽  
Sex Determination ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Apparent Effect ◽  
Linked Gene ◽  
Male Development ◽  
Coordinate Control

Abstract We have identified a new X-linked gene, sdc-2, that controls the hermaphrodite (XX) modes of both sex determination and X chromosome dosage compensation in Caenorhabditis elegans. Mutations in sdc-2 cause phenotypes that appear to result from a shift of both the sex determination and dosage compensation processes in XX animals to the XO modes of expression. Twenty-eight independent sdc-2 mutations have no apparent effect in XO animals, but cause two distinct phenotypes in XX animals: masculinization, reflecting a defect in sex determination, and lethality or dumpiness, reflecting a disruption in dosage compensation. The dosage compensation defect can be demonstrated directly by showing that sdc-2 mutations cause elevated levels of several X-linked transcripts in XX but not XO animals. While the masculinization is blocked by mutations in sex determining genes required for male development (her-1 and fem-3), the lethality, dumpiness and overexpression of X-linked genes are not, indicating that the effect of sdc-2 mutations on sex determination and dosage compensation are ultimately implemented by two independent pathways. We propose a model in which sdc-2 is involved in the coordinate control of both sex determination and dosage compensation in XX animals and acts in the regulatory hierarchy at a step prior to the divergence of the two pathways.

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 The Influence of Chromosomal Environment on X-Linked Gene Expression in Drosophila melanogaster

2020 ◽  
Vol 12 (12) ◽  
pp. 2391-2402
Author(s):  
Aleksei Belyi ◽  
Eliza Argyridou ◽  
John Parsch
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Binding Site ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Negative Correlation ◽  
Expression Ratio ◽  
Linked Gene ◽  
Somatic Tissues ◽  
Male To Female

Abstract Sex chromosomes often differ from autosomes with respect to their gene expression and regulation. In Drosophila melanogaster, X-linked genes are dosage compensated by having their expression upregulated in the male soma, a process mediated by the X-chromosome-specific binding of the dosage compensation complex (DCC). Previous studies of X-linked gene expression found a negative correlation between a gene’s male-to-female expression ratio and its distance to the nearest DCC binding site in somatic tissues, including head and brain, which suggests that dosage compensation influences sex-biased gene expression. A limitation of the previous studies, however, was that they focused on endogenous X-linked genes and, thus, could not disentangle the effects of chromosomal position from those of gene-specific regulation. To overcome this limitation, we examined the expression of an exogenous reporter gene inserted at many locations spanning the X chromosome. We observed a negative correlation between the male-to-female expression ratio of the reporter gene and its distance to the nearest DCC binding site in somatic tissues, but not in gonads. A reporter gene’s location relative to a DCC binding site had greater influence on its expression than the local regulatory elements of neighboring endogenous genes, suggesting that intra-chromosomal variation in the strength of dosage compensation is a major determinant of sex-biased gene expression. Average levels of sex-biased expression did not differ between head and brain, but there was greater positional effect variation in the brain, which may explain the observed excess of endogenous sex-biased genes located on the X chromosome in this tissue.

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