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Judith E Mank - One of the best experts on this subject based on the ideXlab platform.
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Rapid Evolution of Complete Dosage Compensation in Poecilia
'Oxford University Press (OUP)', 2021Co-Authors: Metzger Dch, Ba Sandkam, Judith E MankAbstract:This is the final version. Available from Oxford University Press / Society for Molecular Biology and Evolution via the DOI in this record. RNA-sequencing data generated for this project have been made available to download from the NCBI sequence read archive under BioProject accession PRJNA741270.Dosage Compensation balances gene expression between the sexes in systems with diverged heterogametic sex chromosomes. Theory predicts that Dosage Compensation should rapidly evolve in tandem with the divergence of sex chromosomes to prevent the deleterious effects of Dosage imbalances that occur as a result of sex chromosome divergence. Examples of complete Dosage Compensation, where gene expression of the entire sex chromosome is compensated, are rare, and have only been found in relatively ancient sex chromosome systems. Consequently, very little is known about the evolutionary dynamics of complete Dosage Compensation systems. Within the family Poeciliidae the subgenus Lebistes share the same sex chromosome system which originated 18.48-26.08 Ma. In Poecilia reticulata and P. wingei, the Y chromosome has been largely maintained, whereas the Y in the closely related species P. picta and P. parae has rapidly degraded. We recently found P. picta to be the first example of complete Dosage Compensation in a fish. Here, we show that P. parae also has complete Dosage Compensation, thus complete Dosage Compensation likely evolved in the short (∼3.7 Myr) interval after the split of the ancestor of these two species from P. reticulata, but before they diverged from each other. These data suggest that novel Dosage Compensation mechanisms can evolve rapidly, thus supporting the longstanding theoretical prediction that such mechanisms arise in tandem with rapidly diverging sex chromosomes.European Research Council (ERC)Canada 150 Research Chair ProgramNSER
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sex chromosome Dosage Compensation definitely not for everyone
Trends in Genetics, 2013Co-Authors: Judith E MankAbstract:Sex chromosomes often entail gene dose differences between the sexes, which if not compensated for, lead to differences between males and females in the expression of sex-linked genes. Recent work has shown that different organisms respond to sex chromosome dose in a variety of ways, ranging from complete sex chromosome Dosage Compensation in some species to active Compensation of only a minority genes in other organisms. Although we still do not understand the implications of the diversity in sex chromosome Dosage Compensation, its realization has created exciting new opportunities to study the evolution, mechanism, and consequences of gene regulation. However, confusion remains as to what sorts of genes are likely to be Dosage compensated, how Dosage Compensation evolves, and why complete Dosage Compensation appears to be limited to male heterogametic species. In this review, I survey the status of Dosage Compensation to answer these questions and identify current controversies in this fast-moving field.
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trade off between selection for Dosage Compensation and masculinization on the avian z chromosome
Genetics, 2012Co-Authors: Alison E Wright, Hooman K Moghadam, Judith E MankAbstract:Following the suppression of recombination, gene expression levels decline on the sex-limited chromosome, and this can lead to selection for Dosage Compensation in the heterogametic sex to rebalance average expression from the X or Z chromosome with average autosomal expression. At the same time, due to their unequal pattern of inheritance in males and females, the sex chromosomes are subject to unbalanced sex-specific selection, which contributes to a nonrandom distribution of sex-biased genes compared to the remainder of the genome. These two forces act against each other, and the relative importance of each is currently unclear. The Gallus gallus Z chromosome provides a useful opportunity to study the importance and trade-offs between sex-specific selection and Dosage Compensation in shaping the evolution of the genome as it shows incomplete Dosage Compensation and is also present twice as often in males than females, and therefore predicted to be enriched for male-biased genes. Here, we refine our understanding of the evolution of the avian Z chromosome, and show that multiple strata formed across the chromosome over ∼130 million years. We then use this evolutionary history to examine the relative strength of selection for sex chromosome Dosage Compensation vs. the cumulative effects of masculinizing selection on gene expression. We find that male-biased expression increases over time, indicating that selection for Dosage Compensation is relatively less important than masculinizing selection in shaping Z chromosome gene expression.
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incomplete sex chromosome Dosage Compensation in the indian meal moth plodia interpunctella based on de novo transcriptome assembly
Genome Biology and Evolution, 2012Co-Authors: Peter W Harrison, Judith E Mank, Nina WedellAbstract:Males and females experience differences in gene dose for loci in the nonrecombining region of heteromorphic sex chromosomes. If not compensated, this leads to expression imbalances, with the homogametic sex on average exhibiting greater expression due to the doubled gene dose. Many organisms with heteromorphic sex chromosomes display global Dosage Compensation mechanisms, which equalize gene expression levels between the sexes. However, birds and Schistosoma have been previously shown to lack chromosome-wide Dosage Compensation mechanisms, and the status in other female heterogametic taxa including Lepidoptera remains unresolved. To further our understanding of Dosage Compensation in female heterogametic taxa and to resolve its status in the lepidopterans, we assessed the Indian meal moth, Plodia interpunctella. As P. interpunctella lacks a complete reference genome, we conducted de novo transcriptome assembly combined with orthologous genomic location prediction from the related silkworm genome, Bombyx mori, to compare Z-linked and autosomal gene expression levels for each sex. We demonstrate that P. interpunctella lacks complete Z chromosome Dosage Compensation, female Z-linked genes having just over half the expression level of males and autosomal genes. This finding suggests that the Lepidoptera and possibly all female heterogametic taxa lack global Dosage Compensation, although more species will need to be sampled to confirm this assertion.
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some inconvenient truths about sex chromosome Dosage Compensation and the potential role of sexual conflict
Evolution, 2011Co-Authors: Judith E Mank, David J Hosken, Nina WedellAbstract:Sex chromosome Dosage Compensation was once thought to be required to balance gene expression levels between sex-linked and autosomal genes in the heterogametic sex. Recent evidence from a range of animals has indicated that although sex chromosome Dosage Compensation exists in some clades, it is far from a necessary companion to sex chromosome evolution, and is in fact rather rare in animals. This raises questions about why complex Dosage Compensation mechanisms arise in some clades when they are not strictly needed, and suggests that the role of sex-specific selection in sex chromosome gene regulation should be reassessed. We show there exists a tremendous diversity in the mechanisms that regulate gene Dosage and argue that sexual conflict may be an overlooked agent responsible for some of the variation seen in sex chromosome gene dose regulation.
Doris Bachtrog - One of the best experts on this subject based on the ideXlab platform.
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contingency in the convergent evolution of a regulatory network Dosage Compensation in drosophila
PLOS Biology, 2019Co-Authors: Christopher E Ellison, Doris BachtrogAbstract:The repeatability or predictability of evolution is a central question in evolutionary biology and most often addressed in experimental evolution studies. Here, we infer how genetically heterogeneous natural systems acquire the same molecular changes to address how genomic background affects adaptation in natural populations. In particular, we take advantage of independently formed neo-sex chromosomes in Drosophila species that have evolved Dosage Compensation by co-opting the Dosage-Compensation male-specific lethal (MSL) complex to study the mutational paths that have led to the acquisition of hundreds of novel binding sites for the MSL complex in different species. This complex recognizes a conserved 21-bp GA-rich sequence motif that is enriched on the X chromosome, and newly formed X chromosomes recruit the MSL complex by de novo acquisition of this binding motif. We identify recently formed sex chromosomes in the D. melanica and D. robusta species groups by genome sequencing and generate genomic occupancy maps of the MSL complex to infer the location of novel binding sites. We find that diverse mutational paths were utilized in each species to evolve hundreds of de novo binding motifs along the neo-X, including expansions of microsatellites and transposable element (TE) insertions. However, the propensity to utilize a particular mutational path differs between independently formed X chromosomes and appears to be contingent on genomic properties of that species, such as simple repeat or TE density. This establishes the “genomic environment” as an important determinant in predicting the outcome of evolutionary adaptations.
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Dosage Compensation and neo-sex chromosomes in Drosophila.
2019Co-Authors: Christopher Ellison, Doris BachtrogAbstract:(A) MSL-mediated Dosage Compensation in Drosophila. The MSL complex consists of several proteins and noncoding RNAs (roX RNAs) and targets the X chromosome at CESs that contain the MSL-binding motif (as GA-rich sequence motif). (B) Formation of neo-sex chromosomes in Drosophila. The ancestral karyotype of Drosophila consists of five large rods (the ancestral X, which is conserved across Drosophila, and the autosomal arms Muller element B, C, D, and E) and the small dot chromosome (Muller element F). Autosomes repeatedly fused to the sex chromosomes, forming neo-X and neo-Y chromosomes. Loss of genes on the neo-Y creates selective pressure to Dosage compensate neo-X genes and has repeatedly evolved in Drosophila by co-opting the MSL complex through the acquisition of novel MSL-binding sites. (C) ChIRP can be used to identify MSL-binding sites on Drosophila sex chromosomes. The roX RNA is bound in vivo to CESs; chromatin is cross-linked and fragmented, and roX2 is affinity purified and sequenced. CES, chromatin entry site; ChIRP, Chromatin Isolation by RNA Purification; MSL, male-specific lethal.
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contingency in the convergent evolution of a regulatory network Dosage Compensation in drosophila
bioRxiv, 2018Co-Authors: Doris Bachtrog, Christopher E EllisonAbstract:The repeatability or predictability of evolution is a central question in evolutionary biology, and most often addressed in experimental evolution studies. Here, we infer how genetically heterogeneous natural systems acquire the same molecular changes, to address how genomic background affects adaptation in natural populations. In particular, we take advantage of independently formed neo-sex chromosomes in Drosophila species that have evolved Dosage Compensation by co-opting the Dosage Compensation (MSL) complex, to study the mutational paths that have led to the acquisition of 100s of novel binding sites for the MSL complex in different species. This complex recognizes a conserved 21-bp GA-rich sequence motif that is enriched on the X chromosome, and newly formed X chromosomes recruit the MSL complex by de novo acquisition of this binding motif. We identify recently formed sex chromosomes in the Drosophila repleta and robusta species groups by genome sequencing, and generate genomic occupancy maps of the MSL complex to infer the location of novel binding sites. We find that diverse mutational paths were utilized in each species to evolve 100s of de novo binding motifs along the neo-X, including expansions of microsatellites and transposable element insertions. However, the propensity to utilize a particular mutational path differs between independently formed X chromosomes, and appears to be contingent on genomic properties of that species, such as simple repeat or transposable element density. This establishes the “genomic environment” as an important determinant in predicting the outcome of evolutionary adaptations.
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partial Dosage Compensation in strepsiptera a sister group of beetles
Genome Biology and Evolution, 2015Co-Authors: Shivani Mahajan, Doris BachtrogAbstract:Sex chromosomes have evolved independently in many different taxa, and so have mechanisms to compensate for expression differences on sex chromosomes in males and females. Different clades have evolved vastly different ways to achieve Dosage Compensation, including hypertranscription of the single X in male Drosophila, downregulation of both X’s in XX Caenorhabditis, or inactivation of one X in female mammals. In the flour beetle Tribolium, the X appears hyperexpressed in both sexes, which might represent the first of two steps to evolve Dosage Compensation along the paths mammals may have taken (i.e., upregulation of X in both sexes, followed by inactivation of one X in females). Here we test for Dosage Compensation in Strepsiptera, a sister taxon to beetles. We identify sex-linked chromosomes in Xenos vesparum based on genomic analysis of males and females, and show that its sex chromosome consists of two chromosomal arms in Tribolium: The X chromosome that is shared between Tribolium and Strepsiptera, and another chromosome that is autosomal in Tribolium and another distantly related Strepsiptera species, but sex-linked in X. vesparum. We use RNA-seq (RNA sequencing) to show that Dosage Compensation along the X of X. vesparum is partial and heterogeneous. In particular, genes that are X-linked in both beetles and Strepsiptera appear fully Dosage compensated probably through downregulation in both sexes, whereas genes on the more recently added X segment have evolved only partial Dosage Compensation. In addition, reanalysis of published RNA-seq data suggests that Tribolium has evolved Dosage Compensation, without hypertranscribing the X in females. Our results demonstrate that patterns of Dosage Compensation are highly variable across sex-determination systems and even within species.
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the epigenome of evolving drosophila neo sex chromosomes Dosage Compensation and heterochromatin formation
PLOS Biology, 2013Co-Authors: Qi Zhou, Christopher E Ellison, Vera B Kaiser, Artyom A Alekseyenko, Andrey A Gorchakov, Doris BachtrogAbstract:Sex chromosomes originated from autosomes but have evolved a highly specialized chromatin structure. Drosophila Y chromosomes are composed entirely of silent heterochromatin, while male X chromosomes have highly accessible chromatin and are hypertranscribed as a result of Dosage Compensation. Here, we dissect the molecular mechanisms and functional pressures driving heterochromatin formation and Dosage Compensation of the recently formed neo-sex chromosomes of Drosophila miranda. We show that the onset of heterochromatin formation on the neo-Y is triggered by an accumulation of repetitive DNA. The neo-X has evolved partial Dosage Compensation and we find that diverse mutational paths have been utilized to establish several dozen novel binding consensus motifs for the Dosage Compensation complex on the neo-X, including simple point mutations at pre-binding sites, insertion and deletion mutations, microsatellite expansions, or tandem amplification of weak binding sites. Spreading of these silencing or activating chromatin modifications to adjacent regions results in massive mis-expression of neo-sex linked genes, and little correspondence between functionality of genes and their silencing on the neo-Y or Dosage Compensation on the neo-X. Intriguingly, the genomic regions being targeted by the Dosage Compensation complex on the neo-X and those becoming heterochromatic on the neo-Y show little overlap, possibly reflecting different propensities along the ancestral chromosome that formed the sex chromosome to adopt active or repressive chromatin configurations. Our findings have broad implications for current models of sex chromosome evolution, and demonstrate how mechanistic constraints can limit evolutionary adaptations. Our study also highlights how evolution can follow predictable genetic trajectories, by repeatedly acquiring the same 21-bp consensus motif for recruitment of the Dosage Compensation complex, yet utilizing a diverse array of random mutational changes to attain the same phenotypic outcome.
Mitzi I Kuroda - One of the best experts on this subject based on the ideXlab platform.
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sex specific phenotypes of histone h4 point mutants establish Dosage Compensation as the critical function of h4k16 acetylation in drosophila
Proceedings of the National Academy of Sciences of the United States of America, 2018Co-Authors: Omer Copur, Mitzi I Kuroda, Andrey A Gorchakov, Katja Finkl, Jurg MullerAbstract:Acetylation of histone H4 at lysine 16 (H4K16) modulates nucleosome–nucleosome interactions and directly affects nucleosome binding by certain proteins. In Drosophila , H4K16 acetylation by the Dosage Compensation complex subunit Mof is linked to increased transcription of genes on the single X chromosome in males. Here, we analyzed Drosophila containing different H4K16 mutations or lacking Mof protein. An H4K16A mutation causes embryonic lethality in both sexes, whereas an H4K16R mutation permits females to develop into adults but causes lethality in males. The acetyl-mimic mutation H4K16Q permits both females and males to develop into adults. Complementary analyses reveal that males lacking maternally deposited and zygotically expressed Mof protein arrest development during gastrulation, whereas females of the same genotype develop into adults. Together, this demonstrates the causative role of H4K16 acetylation by Mof for Dosage Compensation in Drosophila and uncovers a previously unrecognized requirement for this process already during the onset of zygotic gene transcription.
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x chromosome Dosage Compensation via enhanced transcriptional elongation in drosophila
Nature, 2011Co-Authors: Erica Larschan, Eric P Bishop, Peter V Kharchenko, Leighton J Core, John T Lis, Peter J Park, Mitzi I KurodaAbstract:Different organisms use a variety of mechanisms to compensate for X chromosome Dosage imbalance between the sexes. In Drosophila, the MSL (Male-specific lethal) complex increases transcription on the single X chromosome of males and is thought to regulate transcription elongation, although mechanistic details have been unclear. A global run-on sequencing technique has now been used to reveal that the MSL complex seems to enhance transcription by facilitating the progression of RNA polymerase II across the bodies of active X-linked genes. In this way, MSL can impose Dosage Compensation on diverse genes with a wide range of transcription levels along the X chromosome. Different organisms use a variety of mechanisms to compensate for X chromosome Dosage imbalance between the sexes. In Drosophila, the MSL complex increases transcription on the single X chromosome of males and is thought to regulate transcription elongation, although mechanistic details have been unclear. Here, a global run-on sequencing technique is used to reveal that the MSL complex seems to enhance transcription by facilitating the progression of RNA polymerase II across the bodies of active X linked genes. In this way, MSL can impose Dosage Compensation on diverse genes with a wide range of transcription levels along the X chromosome. The evolution of sex chromosomes has resulted in numerous species in which females inherit two X chromosomes but males have a single X, thus requiring Dosage Compensation. MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males to equalize expression of X-linked genes between the sexes1. The biochemical mechanisms used for Dosage Compensation must function over a wide dynamic range of transcription levels and differential expression patterns. It has been proposed2 that the MSL complex regulates transcriptional elongation to control Dosage Compensation, a model subsequently supported by mapping of the MSL complex and MSL-dependent histone 4 lysine 16 acetylation to the bodies of X-linked genes in males, with a bias towards 3′ ends3,4,5,6,7. However, experimental analysis of MSL function at the mechanistic level has been challenging owing to the small magnitude of the chromosome-wide effect and the lack of an in vitro system for biochemical analysis. Here we use global run-on sequencing (GRO-seq)8 to examine the specific effect of the MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that the MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific controls may explain how Dosage Compensation can be imposed on the diverse set of genes along an entire chromosome.
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acetylated histone h4 on the male x chromosome is associated with Dosage Compensation in drosophila
Genes & Development, 1994Co-Authors: James R Bone, J Lavender, Ron Richman, M J Palmer, Bryan M Turner, Mitzi I KurodaAbstract:Dosage Compensation in Drosophila occurs by an increase in transcription of genes on the X chromosome in males. This elevated expression requires the function of at least four loci, known collectively as the male-specific lethal (msl) genes. The proteins encoded by two of these genes, maleless (mle) and male-specific lethal-1 (msl-1), are found associated with the X chromosome in males, suggesting that they act as positive regulators of Dosage Compensation. A specific acetylated isoform of histone H4, H4Ac16, is also detected predominantly on the male X chromosome. We have found that MLE and MSL-1 bind to the X chromosome in an identical pattern and that the pattern of H4Ac16 on the X is largely coincident with that of MLE/MSL-1. We fail to detect H4Ac16 on the X chromosome in homozygous msl males, correlating with the lack of Dosage Compensation in these mutants. Conversely, in Sxl mutants, we detect H4Ac16 on the female X chromosomes, coincident with an inappropriate increase in X chromosome transcription. These data suggest that synthesis or localization of H4Ac16 is controlled by the Dosage Compensation regulatory hierarchy. Dosage Compensation may involve H4Ac16 function, potentially through interaction with the product of the msl genes.
Barbara J Meyer - One of the best experts on this subject based on the ideXlab platform.
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condensin controls recruitment of rna polymerase ii to achieve nematode x chromosome Dosage Compensation
eLife, 2013Co-Authors: William S Kruesi, John T Lis, Leighton J Core, Colin T Waters, Barbara J MeyerAbstract:The X-chromosome gene regulatory process called Dosage Compensation ensures that males (1X) and females (2X) express equal levels of X-chromosome transcripts. The mechanism in Caenorhabditis elegans has been elusive due to improperly annotated transcription start sites (TSSs). Here we define TSSs and the distribution of transcriptionally engaged RNA polymerase II (Pol II) genome-wide in wild-type and Dosage-Compensation-defective animals to dissect this regulatory mechanism. Our TSS-mapping strategy integrates GRO-seq, which tracks nascent transcription, with a new derivative of this method, called GRO-cap, which recovers nascent RNAs with 5′ caps prior to their removal by co-transcriptional processing. Our analyses reveal that promoter-proximal pausing is rare, unlike in other metazoans, and promoters are unexpectedly far upstream from the 5′ ends of mature mRNAs. We find that C. elegans equalizes X-chromosome expression between the sexes, to a level equivalent to autosomes, by reducing Pol II recruitment to promoters of hermaphrodite X-linked genes using a chromosome-restructuring condensin complex. DOI: http://dx.doi.org/10.7554/eLife.00808.001
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meiotic crossover number and distribution are regulated by a Dosage Compensation protein that resembles a condensin subunit
Genes & Development, 2008Co-Authors: Chun J Tsai, Michael R Albrecht, David G Mets, Paola Nix, Annette Chan, Barbara J MeyerAbstract:Biological processes that function chromosome-wide are not well understood. Here, we show that the Caenorhabditis elegans protein DPY-28 controls two such processes, X-chromosome Dosage Compensation in somatic cells and meiotic crossover number and distribution in germ cells. DPY-28 resembles a subunit of condensin, a conserved complex required for chromosome compaction and segregation. In the soma, DPY-28 associates with the Dosage Compensation complex on hermaphrodite X chromosomes to repress transcript levels. In the germline, DPY-28 restricts crossovers. In many organisms, one crossover decreases the likelihood of another crossover nearby, an enigmatic process called crossover interference. In C. elegans, interference is complete: Only one crossover occurs per homolog pair. dpy-28 mutations increase crossovers, disrupt crossover interference, and alter crossover distribution. Early recombination intermediates (RAD-51 foci) increase concomitantly, suggesting that DPY-28 acts to limit double-strand breaks (DSBs). Reinforcing this view, dpy-28 mutations partially restore DSBs in mutants lacking HIM-17, a chromatin-associated protein required for DSB formation. Our work further links Dosage Compensation to condensin and establishes a new role for condensin components in regulating crossover number and distribution. We propose that both processes utilize a related mechanism involving changes in higher-order chromosome structure to achieve chromosome-wide effects.
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Dosage Compensation proteins targeted to x chromosomes by a determinant of hermaphrodite fate
Science, 1999Co-Authors: Heather Dawes, Dorit S Berlin, Denise M Lapidus, Chad Nusbaum, Tamara L Davis, Barbara J MeyerAbstract:In many organisms, master control genes coordinately regulate sex-specific aspects of development. SDC-2 was shown to induce hermaphrodite sexual differentiation and activate X chromosome Dosage Compensation in Caenorhabditis elegans. To control these distinct processes, SDC-2 acts as a strong gene-specific repressor and a weaker chromosome-wide repressor. To initiate hermaphrodite development, SDC-2 associates with the promoter of the male sex-determining gene her-1 to repress its transcription. To activate Dosage Compensation, SDC-2 triggers assembly of a specialized protein complex exclusively on hermaphrodite X chromosomes to reduce gene expression by half. SDC-2 can localize to X chromosomes without other components of the Dosage Compensation complex, suggesting that SDC-2 targets Dosage Compensation machinery to X chromosomes.
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mix 1 an essential component of the c elegans mitotic machinery executes x chromosome Dosage Compensation
Cell, 1998Co-Authors: Jason D Lieb, Michael R Albrecht, Paotien Chuang, Barbara J MeyerAbstract:We show that a functional component of the C. elegans mitotic machinery regulates X chromosome gene expression. This protein, MIX-1, is a member of the Dosage Compensation complex that associates specifically with hermaphrodite X chromosomes to reduce their gene expression during interphase. MIX-1 also associates with all mitotic chromosomes to ensure their proper segregation. Both Dosage Compensation and mitosis are severely disrupted by mix-1 mutations. MIX-1 belongs to the SMC protein family required for mitotic chromosome condensation and segregation in yeast and frogs. Thus, an essential, conserved component of mitotic chromosomes has been recruited to the Dosage Compensation process. Rather than Dosage Compensation and mitosis being achieved by two separate sets of related genes, these two processes share an identical component, indicating a common mechanism for establishing higher order chromosome structure and proper X chromosome gene expression.
Peter B Becker - One of the best experts on this subject based on the ideXlab platform.
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progressive Dosage Compensation during drosophila embryogenesis is reflected by gene arrangement
EMBO Reports, 2019Co-Authors: Khairunnadiya Prayitno, Tamas Schauer, Catherine Regnard, Peter B BeckerAbstract:In Drosophila melanogaster males, X-chromosome monosomy is compensated by chromosome-wide transcription activation. We found that complete Dosage Compensation during embryogenesis takes surprisingly long and is incomplete even after 10 h of development. Although the activating Dosage Compensation complex (DCC) associates with the X-chromosome and MOF acetylates histone H4 early, many genes are not compensated. Acetylation levels on gene bodies continue to increase for several hours after gastrulation in parallel with progressive Compensation. Constitutive genes are compensated earlier than developmental genes. Remarkably, later Compensation correlates with longer distances to DCC binding sites. This time-space relationship suggests that DCC action on target genes requires maturation of the active chromosome compartment.
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pionx sites mark the x chromosome for Dosage Compensation
Nature, 2016Co-Authors: Raffaella Villa, Tamas Schauer, Pawel Smialowski, Tobias Straub, Peter B BeckerAbstract:Recognition of the X chromosome by the Dosage Compensation complex in Drosophila relies on the sequence and shape of PionX sites.
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chromosome wide gene specific targeting of the drosophila Dosage Compensation complex
Genes & Development, 2006Co-Authors: Gregor D Gilfillan, Tobias Straub, Elzo De Wit, Frauke Greil, Rosemarie Lamm, Bas Van Steensel, Peter B BeckerAbstract:The Dosage Compensation complex (DCC) of Drosophila melanogaster is capable of distinguishing the single male X from the other chromosomes in the nucleus. It selectively interacts in a discontinuous pattern with much of the X chromosome. How the DCC identifies and binds the X, including binding to the many genes that require Dosage Compensation, is currently unknown. To identify bound genes and attempt to isolate the targeting cues, we visualized male-specific lethal 1 (MSL1) protein binding along the X chromosome by combining chromatin immunoprecipitation with high-resolution microarrays. More than 700 binding regions for the DCC were observed, encompassing more than half the genes found on the X chromosome. In addition, several rare autosomal binding sites were identified. Essential genes are preferred targets, and genes binding high levels of DCC appear to experience the most Compensation (i.e., greatest increase in expression). DCC binding clearly favors genes over intergenic regions, and binds most strongly to the 3' end of transcription units. Within the targeted genes, the DCC exhibits a strong preference for exons and coding sequences. Our results demonstrate gene-specific binding of the DCC, and identify several sequence elements that may partly direct its targeting.
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activation of transcription through histone h4 acetylation by mof an acetyltransferase essential for Dosage Compensation in drosophila
Molecular Cell, 2000Co-Authors: Asifa Akhtar, Peter B BeckerAbstract:Dosage Compensation in Drosophila involves a 2-fold increase in transcription from the single male X relative to the two female X chromosomes. Regulation at the level of the chromosome involves alterations in chromatin organization: male X chromosomes appear decondensed and are marked by acetylation of histone H4 at lysine 16. We demonstrate that MOF, a protein required for Dosage Compensation with significant sequence similarity to the MYST family of acetyltransferases, is a histone acetyltransferase that acetylates chromatin specifically at histone H4 lysine 16. This acetylation relieves chromatin-mediated repression of transcription in vitro and in vivo if MOF is targeted to a promoter by fusion to a DNA-binding domain. Acetylation of chromatin by MOF, therefore, appears to be causally involved in transcriptional activation during Dosage Compensation.
