Multi-level transcriptional regulation of embryonic sex determination and dosage compensation by the X-signal element sex-1
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ABSTRACT:
PROVIDER: PRJNA1165207 | ENA |
REPOSITORIES: ENA
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Project description:The C. elegans nuclear hormone receptor sex-1 is known to be an embryonic X-signal element that represses xol-1, the sex-switch gene that is the master regulator of sex determination and dosage compensation. Several prior studies on sex-1 function have suggested that sex-1 may have additional downstream roles beyond the regulation of xol-1 expression. In this study we characterize some of these additional roles of sex-1 in regulating the dual processes of sex determination and dosage compensation during embryogenesis. Our study reveals that sex-1 acts on many of the downstream targets of xol-1 in a xol-1-independent manner. Further analysis of these shared but independently regulated downstream targets uncovered that sex-1 mediates the expression of hermaphrodite- and male-biased genes during embryogenesis. We validated sex-1 binding on one of these downstream targets, the male-developmental gene her-1. Our data suggests a model where sex-1 exhibits multi-level direct transcriptional regulation on several targets downstream of xol-1 to reinforce the appropriate expression of sex-biased transcripts in XX embryos. Furthermore, we found that xol-1 sex-1 double mutants show defects in dosage compensation. Our study provides evidence that this is caused by the misregulation of dpy-21, one of the components of the dosage compensation complex, and the subsequent misregulation of H4K20me1 enrichment on the X chromosomes.
2025-09-01 | GSE278001 | GEO
Project description:Gene dosage imbalance of heteromorphic sex chromosomes (XY or ZW) exists between the sexes, and with the autosomes. Mammalian X chromosome inactivation was long thought to imply a critical need for dosage compensation in vertebrates. However, mRNA abundance measurements that demonstrated sex chromosome transcripts are neither balanced between the sexes or with autosomes in monotreme mammals or birds brought sex chromosome dosage compensation into question. This study examines transcriptomic and proteomic levels of dosage compensation in platypus and chicken compared to mouse, a model eutherian species. We analyzed mRNA and protein levels in heart and liver tissues of chicken, mouse and platypus.
2024-07-30 | PXD040182 | Pride
Project description:Sex-chromosome dosage represents a challenge for heterogametic species to maintain correct proportion of gene products across chromosomes in each sex. While therian mammals (XX/XY system) achieve near-perfect balance of X-chromosome mRNAs through X-upregulation and X-inactivation, birds (ZW/ZZ system) have been found to lack efficient compensation at RNA level, challenging the necessity of resolving major gene-dosage discrepancies in avian cells. Through allele-resolved multiome analyses, we comprehensively examined dosage compensation in female (ZW), male (ZZ), and rare intersex (ZZW) chicken. Remarkably, this revealed that females exhibit upregulation of their single Z through increased transcriptional burst frequency similar to mammalian X-upregulation, and that Z-protein levels are further balanced via enhanced translation efficiency in females. Global analyses of transcriptional kinetics elements in birds demonstrate remarkable conservation of the genomic encoding of burst kinetics between mammals and birds. Our study uncovers new mechanisms for achieving sex-chromosome dosage compensation and highlights the importance of gene-dosage balance across diverse species.
2025-08-22 | PXD054989 | Pride
Project description:The Anopheles mosquito is one of thousands of species in which sex differences play a central role in their biology, as only females need a blood meal in order to produce eggs. Sex differentiation is regulated by sex chromosomes, but their presence creates a dosage imbalance between males (XY) and females (XX). Dosage compensation (DC) can re-equilibrate the expression of sex-chromosomal genes, but because the molecular mechanisms providing DC have only been studied in a few model organisms, key questions about its evolutionary diversity and functional necessity remain unresolved. Here, we reveal the DC pathway in the malaria mosquito Anopheles gambiae. We identified SOA, a previously uncharacterized gene, whose expression is sufficient to induce a global upregulation of X-linked genes. Sex-specific alternative splicing prevents the production of a functional SOA protein in females. The male SOA isoform encodes a DNA-binding protein that recognizes the promoters of X chromosomal genes through a CA repeat sequence. Male mosquitos lacking SOA exhibit a chromosome-wide downregulation of the X, which is compatible with viability, but causes a developmental delay. Thus, our molecular analysis of the first DC master regulator in a non-model organism elucidates the evolutionary steps leading to the establishment of a chromosome-specific fine-tuning mechanism.
2023-07-13 | PXD042353 | Pride
Project description:Sex in birds is genetically determined, molecular mechanism of which is not well-understood. Their Z sex chromosome (chrZ) lacks whole chromosome inactivation as known for mammalian chrX. To investigate the extent of chrZ dosage compensation and its role in somatic cell’s sex specification, we used a highly-quantitative method and analyzed transcriptional activities of male and female fibroblasts from seven birds. Our data indicate for the first time that ¾ of chrZ genes are strictly compensated, similar to that observed in chrX. We also describe non-compensated chrZ genes and identify Ribosomal Protein S6 (RPS6) as a candidate for universal, sex-dimorphic genes in birds.
2023-08-30 | GSE213253 | GEO
Project description:Using 4 replicate males and 4 replicate females this experiment examined dosage compensation and sex-biased gene expression. Briefly we performed a de novo assembly of the Manduca sexta transcriptome using all sequenced libraries, quantified genes expression, identified the physical locations of genes through orthology to the moth Bombyx mori and examine expression differences between autosomal and Z-linked genes between males and females. Further, we examined sex-biased gene expression using the replicated data.
2014-03-18 | E-MTAB-2066 | biostudies-arrayexpress
Project description:Sex determination is still poorly understood in birds and no key determinants have so far been identified. In contrast to most other species, dosage compensation of bird sex chromosomal genes appears rather ineffective. By comparing microarrays of microdissected primitive streak from single chicken embryos, we identified a large number of genes differentially expressed between male and female embryos at a very early stage (Hamburger and Hamilton stage 4), long before any sexual differentiation occurs. Most of these genes are located on the Z chromosome, which indicates that dosage compensation is ineffective in early chicken embryos. Gene ontology analyses using an enhanced annotation tool for Affymetrix probesets of the chicken genome shows that among the male-biased genes found on the Z chromosome, more than 20 genes have a role in sex differentiation.
2009-05-13 | GSE16064 | GEO
Project description:Birds have a sex chromosome system in which females are heterogametic (ZW) and males are homogametic (ZZ). The differentiation of avian sex chromosomes from ancestral autosomes entailed the loss of most genes from the W chromosome during evolution. However, to what extent mechanisms evolved that counterbalance the consequences of this extensive gene dosage reduction in female birds has remained unclear. Here we report functional in vivo and evolutionary analyses of a Z-chromosome-linked microRNA (miR-2954) with strongly male-biased expression that was previously proposed to play a key role in sex chromosome dosage compensation1. We knocked out miR-2954 in chicken, which resulted in early embryonic lethality of homozygous knockout males, likely due to the highly specific upregulation of dosage-sensitive Z-linked target genes of miR-2954. Our evolutionary gene expression analyses further revealed that these dosage-sensitive target genes have become upregulated on the single Z in female birds during evolution. Altogether, our work unveils a scenario where evolutionary pressures on females following W gene loss led to the evolution of transcriptional upregulation of dosage-sensitive genes on the Z not only in female but also in male birds. The resulting overabundance of transcripts in males resulting from the combined activity of two dosage-sensitive Z gene copies was in turn offset by the emergence of a highly targeted miR-2954-mediated transcript degradation mechanism during avian evolution. Our findings demonstrate that birds have evolved a unique sex chromosome dosage compensation system in which a microRNA has become essential for male survival.
2024-04-17 | GSE257549 | GEO
Project description:Dosage compensation of Z sex chromosome genes in avian fibroblast cells
| PRJNA880269 | ENA
Project description:Complete dosage compensation and sex-biased gene expression in Manduca sexta
| PRJEB4959 | ENA