scholarly journals Interaction of Male Specific Lethal complex and genomic imbalance on global gene expression in Drosophila

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuai Zhang ◽  
Haizhu Qi ◽  
Cheng Huang ◽  
Lijia Yuan ◽  
Ludan Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sexual Dimorphism ◽  
De Novo ◽  
Global Gene Expression ◽  
Dosage Effect ◽  
Specific Response ◽  
X Chromosomes ◽  
Genomic Imbalance ◽  
Msl Complex ◽  
Male Specific

AbstractThe inverse dosage effect caused by chromosome number variations shows global consequences in genomic imbalance including sexual dimorphism and an X chromosome-specific response. To investigate the relationship of the MSL complex to genomic imbalance, we over-expressed MSL2 in autosomal and sex chromosomal aneuploids, and analyzed the different transcriptomes. Some candidate genes involved in regulatory mechanisms have also been tested during embryogenesis using TSA-FISH. Here we show that the de novo MSL complex assembled on the X chromosomes in females further reduced the global expression level on the basis of 2/3 down-regulation caused by the inverse dosage effect in trisomy through epigenetic modulations rather than induced dosage compensation. Plus, the sexual dimorphism effect in unbalanced genomes was further examined due to the pre-existing of the MSL complex in males. All these results demonstrate the dynamic functions of the MSL complex on global gene expression in different aneuploid genomes.

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 Contingency in the convergent evolution of a regulatory network: Dosage compensation in Drosophila

2018 ◽  
Author(s):  
Doris Bachtrog ◽  
Chris Ellison
Keyword(s):  
Transposable Element ◽  
Dosage Compensation ◽  
Sex Chromosomes ◽  
Binding Sites ◽  
Evolutionary Biology ◽  
De Novo ◽  
Binding Motif ◽  
Sequence Motif ◽  
X Chromosomes ◽  
Msl Complex

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.

Drosophila Male-Specific Lethal 2 Protein Controls Sex-Specific Expression of the roX Genes

Genetics ◽  
2004 ◽  
Vol 166 (4) ◽  
pp. 1825-1832 ◽  
Author(s):  
Barbara P Rattner ◽  
Victoria H Meller
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
X Chromosome ◽  
Specific Expression ◽  
Linked Gene ◽  
Male And Female ◽  
Male Specific Lethal ◽  
Msl Complex ◽  
Male Specific ◽  
Rox Rna

Abstract The MSL complex of Drosophila upregulates transcription of the male X chromosome, equalizing male and female X-linked gene expression. Five male-specific lethal proteins and at least one of the two noncoding roX RNAs are essential for this process. The roX RNAs are required for the localization of MSL complexes to the X chromosome. Although the mechanisms directing targeting remain speculative, the ratio of MSL protein to roX RNA influences localization of the complex. We examine the transcriptional regulation of the roX genes and show that MSL2 controls male-specific roX expression in the absence of any other MSL protein. We propose that this mechanism maintains a stable MSL/roX ratio that is favorable for localization of the complex to the X chromosome.

scholarly journals Modulation of Global Gene Expression by Aneuploidy and CNV of Dosage Sensitive Regulatory Genes

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1606
Author(s):  
Shuai Zhang ◽  
Ruixue Wang ◽  
Cheng Huang ◽  
Ludan Zhang ◽  
Lin Sun
Keyword(s):  
Gene Expression ◽  
Sex Chromosome ◽  
Global Gene Expression ◽  
Regulatory Genes ◽  
Dosage Effect ◽  
Macromolecular Complex ◽  
Sequencing Data ◽  
Genome Wide ◽  
A Genome ◽  
Modulation Of Gene Expression

Aneuploidy, which disrupts the genetic balance due to partial genome dosage changes, is usually more detrimental than euploidy variation. To investigate the modulation of gene expression in aneuploidy, we analyzed the transcriptome sequencing data of autosomal and sex chromosome trisomy in Drosophila. The results showed that most genes on the varied chromosome (cis) present dosage compensation, while the remainder of the genome (trans) produce widespread inverse dosage effects. Some altered functions and pathways were identified as the common characteristics of aneuploidy, and several possible regulatory genes were screened for an inverse dosage effect. Furthermore, we demonstrated that dosage changes of inverse regulator Inr-a/pcf11 can produce a genome-wide inverse dosage effect. All these findings suggest that the mechanism of genomic imbalance is related to the changes in the stoichiometric relationships of macromolecular complex members that affect the overall function. These studies may deepen the understanding of gene expression regulatory mechanisms.

scholarly journals Are we there yet? Initial targeting of the Male-Specific Lethal and Polycomb group chromatin complexes in Drosophila

Open Biology ◽  
2014 ◽  
Vol 4 (3) ◽  
pp. 140006 ◽  
Author(s):  
Kyle A. McElroy ◽  
Hyuckjoon Kang ◽  
Mitzi I. Kuroda
Keyword(s):  
Gene Expression ◽  
High Resolution ◽  
Biochemical Properties ◽  
Polycomb Group ◽  
Chromatin Binding ◽  
Male Specific Lethal ◽  
Msl Complex ◽  
Sites Of Action ◽  
Male Specific ◽  
Multicellular Organisms

Chromatin-binding proteins must navigate the complex nuclear milieu to find their sites of action, and a constellation of protein factors and other properties are likely to influence targeting specificity. Despite considerable progress, the precise rules by which binding specificity is achieved have remained elusive. Here, we consider early targeting events for two groups of chromatin-binding complexes in Drosophila : the Male-Specific Lethal (MSL) and the Polycomb group (PcG) complexes. These two serve as models for understanding targeting, because they have been extensively studied and play vital roles in Drosophila , and their targets have been documented at high resolution. Furthermore, the proteins and biochemical properties of both complexes are largely conserved in multicellular organisms, including humans. While the MSL complex increases gene expression and PcG members repress genes, the two groups share many similarities such as the ability to modify their chromatin environment to create active or repressive domains, respectively. With legacies of in-depth genetic, biochemical and now genomic approaches, the MSL and PcG complexes will continue to provide tractable systems for understanding the recruitment of multiprotein chromatin complexes to their target loci.

scholarly journals Male-specific IL-33 expression regulates sex-dimorphic EAE susceptibility

2018 ◽  
Vol 115 (7) ◽  
pp. E1520-E1529 ◽  
Author(s):  
Abigail E. Russi ◽  
Mark E. Ebel ◽  
Yuchen Yang ◽  
Melissa A. Brown
Keyword(s):  
Gene Expression ◽  
Mast Cells ◽  
Demyelinating Disease ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Specific Response ◽  
Autoimmune Encephalomyelitis ◽  
Male Specific ◽  
Experimental Autoimmune

The cellular and molecular basis of sex-dimorphic autoimmune diseases, such as the CNS demyelinating disease multiple sclerosis (MS), remains unclear. Our studies in the SJL mouse model of MS, experimental autoimmune encephalomyelitis (EAE), reveal that sex-determined differences in Il33 expression by innate immune cells in response to myelin peptide immunization regulate EAE susceptibility. IL-33 is selectively induced in PLP139–151-immunized males and activates type 2 innate lymphoid cells (ILC2s), cells that promote and sustain a nonpathogenic Th2 myelin-specific response. Without this attenuating IL-33 response, females generate an encephalitogenic Th17-dominant response, which can be reversed by IL-33 treatment. Mast cells are one source of IL-33 and we provide evidence that testosterone directly induces Il33 gene expression and also exerts effects on the potential for Il33 gene expression during mast cell development. Thus, in contrast to their pathogenic role in allergy, we propose a sex-specific role for both mast cells and ILC2s as attenuators of the pathogenic Th response in CNS inflammatory disease.

scholarly journals De novo compartment deconvolution and weight estimation of tumor samples (DECODER)

2019 ◽  
Author(s):  
Xianlu Laura Peng ◽  
Richard A Moffitt ◽  
Robert J Torphy ◽  
Keith E Volmar ◽  
Jen Jen Yeh
Keyword(s):  
Gene Expression ◽  
De Novo ◽  
Global Gene Expression ◽  
Unknown Primary ◽  
Weight Estimation ◽  
Data Types ◽  
Cellular Compartment ◽  
Cancer Types ◽  
Global Gene Expression Analysis ◽  
Cellular Compartments

AbstractTumors are mixtures of different compartments. While global gene expression analysis profiles the average expression of all compartments in a sample, identifying the specific contribution of each compartment remains a challenge. With the increasing recognition of the importance of non-neoplastic components, the ability to breakdown the gene expression contribution of each is critical. To this end, we developed DECODER, an integrated framework which performs de novo deconvolution, and compartment weight estimation for a single sample. We use DECODER to deconvolve 33 TCGA tumor RNA-seq datasets and show that it may be applied to other data types including ATAC-seq. We demonstrate that it can be utilized to reproducibly estimate cellular compartment weights in pancreatic cancer that are clinically meaningful. Application of DECODER across cancer types advances the capability of identifying cellular compartments in an unknown sample and may have implications for identifying the tumor of origin for cancers of unknown primary.

scholarly journals De novo compartment deconvolution and weight estimation of tumor samples using DECODER

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Xianlu Laura Peng ◽  
Richard A. Moffitt ◽  
Robert J. Torphy ◽  
Keith E. Volmar ◽  
Jen Jen Yeh
Keyword(s):  
Gene Expression ◽  
De Novo ◽  
Global Gene Expression ◽  
Unknown Primary ◽  
Data Sets ◽  
Weight Estimation ◽  
Data Types ◽  
Cancer Types ◽  
Global Gene Expression Analysis ◽  
Cellular Compartments

Abstract Tumors are mixtures of different compartments. While global gene expression analysis profiles the average expression of all compartments in a sample, identifying the specific contribution of each compartment remains a challenge. With the increasing recognition of the importance of non-neoplastic components, the ability to breakdown the gene expression contribution of each is critical. Here, we develop DECODER, an integrated framework which performs de novo deconvolution and single-sample compartment weight estimation. We use DECODER to deconvolve 33 TCGA tumor RNA-seq data sets and show that it may be applied to other data types including ATAC-seq. We demonstrate that it can be utilized to reproducibly estimate cellular compartment weights in pancreatic cancer that are clinically meaningful. Application of DECODER across cancer types advances the capability of identifying cellular compartments in an unknown sample and may have implications for identifying the tumor of origin for cancers of unknown primary.

scholarly journals Use of relevancy and complementary information for discriminatory gene selection from high-dimensional cancer data

2020 ◽  
Author(s):  
Md Nazmul Haque ◽  
Sadia Sharmin ◽  
Amin Ahsan Ali ◽  
Abu Ashfaqur Sajib ◽  
Mohammad Shoyaib
Keyword(s):  
Gene Expression ◽  
Gene Selection ◽  
De Novo ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Poor Performance ◽  
Global Gene Expression ◽  
Biological Information ◽  
Classification Rate ◽  
Cancer Data

AbstractWith the advent of high-throughput technologies, life sciences are generating a huge amount of biomolecular data. Global gene expression profiles provide a snapshot of all the genes that are transcribed or not in a cell or in a tissue at a particular moment under a particular condition. The high-dimensionality of such gene expression data (i.e., very large number of features/genes analyzed in relatively much less number of samples) makes it difficult to identify the key genes (biomarkers) that are truly and more significantly attributing to a particular phenotype or condition, such as cancer or disease, de novo. With the increase in the number of genes, simple feature selection methods show poor performance for both selecting the effective and informative features and capturing biological information. Addressing these issues, here we propose Mutual information based Gene Selection method (MGS) for selecting informative genes and two ranking methods based on frequency (MGSf) and Random Forest (MGSrf) for ranking the selected genes. We tested our methods on four real gene expression datasets derived from different studies on cancerous and normal samples. Our methods obtained better classification rate with the datasets compared to recently reported methods. Our methods could also detect the key relevant pathways with a causal relationship to the phenotype.

scholarly journals The Drosophila Dosage Compensation Complex activates target genes by chromosome looping within the active compartment

2017 ◽  
Author(s):  
Tamás Schauer ◽  
Yad Ghavi-Helm ◽  
Tom Sexton ◽  
Christian Albig ◽  
Catherine Regnard ◽  
...  
Keyword(s):  
Dosage Compensation ◽  
Target Genes ◽  
De Novo ◽  
Gene Activation ◽  
Nuclear Architecture ◽  
Dosage Compensation Complex ◽  
Chromosome Conformation ◽  
X Chromosomes ◽  
Male Specific ◽  
Lethal Dosage

AbstractX chromosome dosage compensation in Drosophila requires chromosome-wide coordination of gene activation. The male-specific-lethal dosage compensation complex (DCC) identifies X chromosomal High Affinity Sites (HAS) from which it boosts transcription. A sub-class of HAS, PionX sites, represent first contacts on the X. Here, we explored the chromosomal interactions of representative PionX sites by high-resolution 4C and determined the global chromosome conformation by Hi-C in sex-sorted embryos. Male and female X chromosomes display similar nuclear architecture, concordant with clustered, constitutively active genes. PionX sites, like HAS, are evenly distributed in the active compartment and engage in short- and long-range interactions beyond compartment boundaries. By de novo induction of DCC in female cells, we monitored the extent of activation surrounding PionX sites. This revealed a remarkable range of DCC action not only in linear proximity, but also at megabase distance if close in space, suggesting that DCC profits from pre-existing chromosome folding to activate genes.

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