Project description:Although sex determination is a fundamental process in vertebrate development, it is very plastic. Diverse genes became major sex determinants in teleost fishes. Deciphering how individual sex-determining genes orchestrate sex determination can reveal new actors in sexual development. Here, we demonstrate that the Y-chromosomal copy of the TGF-β family member gdf6 (gdf6Y) in Nothobranchius furzeri, an emerging model organism in aging research, gained the function of the male sex determinant through allelic diversification while retaining the skeletal developmental function shared with the X-chromosomal gdf6 allele (gdf6X). Concerning sex determination, gdf6Y is expressed by somatic supporting cells of the developing testes. There it induces the male sex in a germ cell-independent manner in contrast to sex determination in zebrafish and the medaka. Looking for downstream effectors of Gdf6Y, we identified besides TGF-β signaling modulators, especially the inhibitor of DNA binding genes id1/2/3, the mRNA decay activator zfp36l2 as a new GDF6 signaling target.
Project description:Although sex determination is a fundamental process in vertebrate development, it is very plastic. Diverse genes became major sex determinants in teleost fishes. Deciphering how individual sex-determining genes orchestrate sex determination can reveal new actors in sexual development. Here, we demonstrate that the Y-chromosomal copy of the TGF-β family member gdf6 (gdf6Y) in Nothobranchius furzeri, an emerging model organism in aging research, gained the function of the male sex determinant through allelic diversification while retaining the skeletal developmental function shared with the X-chromosomal gdf6 allele (gdf6X). Concerning sex determination, gdf6Y is expressed by somatic supporting cells of the developing testes. There it induces the male sex in a germ cell-independent manner in contrast to sex determination in zebrafish and the medaka. Looking for downstream effectors of Gdf6Y, we identified besides TGF-β signaling modulators, especially the inhibitor of DNA binding genes id1/2/3, the mRNA decay activator zfp36l2 as a new GDF6 signaling target.
Project description:Developmental gene expression is defined through cross-talk between the function of transcription factors and epigenetic status including histone modification. Although several known transcription factors play crucial roles in mammalian sex determination, how chromatin regulation contributes to this process is unknown. We observed male-to-female sex reversal in mice lacking the H3K9 demethylase Jmjd1a, and found that Jmjd1a directly regulates expression of the mammalian Y chromosome sex-determining gene Sry, by regulating H3K9me2 marks. These studies reveal a pivotal role for epigenetic regulation in mammalian sex determination, and provide new impetus for identifying additional causes of disorders of sex determination by environmental factors.
Project description:Developmental gene expression is defined through cross-talk between the function of transcription factors and epigenetic status including histone modification. Although several known transcription factors play crucial roles in mammalian sex determination, how chromatin regulation contributes to this process is unknown. We observed male-to-female sex reversal in mice lacking the H3K9 demethylase Jmjd1a, and found that Jmjd1a directly regulates expression of the mammalian Y chromosome sex-determining gene Sry, by regulating H3K9me2 marks. These studies reveal a pivotal role for epigenetic regulation in mammalian sex determination, and provide new impetus for identifying additional causes of disorders of sex determination by environmental factors. Gene expression patterns were measured in gonadal somatic cells of Jmjd1a mutant and control embryos at E11.5. Three biological replicates were performed in each group.
Project description:Purpose: Determine whether sex-determining genes are bivalent at the bipotential stage, poised between the testis and ovary fate, and whether H3K4me3 and H3K27me3 resolve into sex-specific patterns after sex determination, contributing to the canalization and stabilization of either the testis or ovary fate. Methods: XX and XY supporting cells of the gonad were FACS-purified before sex determination (at E10.5) and after sex determination (at E13.5), and submitted to ChIP-seq for H3K4me3, H3K27me3 and H3 as a means to normalize across cell populations. Results: We found that key sex-determining genes are bivalent at the bipotential stage. Genes that are upregulated affter sex determination are stripped of their repressive H3K27me3 mark, whereas repressed genes that promote the alternate pathway remain bivalent even after sex determination.
Project description:The influence of environmental factors, especially temperature, on sex ratio is of great significance to elucidate the mechanism of sex determination. However, the molecular mechanisms by which temperature affects sex determination remains unclear, although a few candidate genes have been found to play a role in the process. In this study, we conducted transcriptome analysis of the effects induced by high temperature on zebrafish during gonad differentiation period. 1171, 1022 and 2921 differentially expressed genes (DEGs) between high temperature and normal temperature were identified at 35, 45 and 60 days post-fertilization (dpf) respectively, revealing that DNA methyltransferases (DNMTs) and heat shock proteins (HSPs) were involved in the heat-exposed sex reversal. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway that were enriched in individuals after heat treatment included Fanconi anemia pathway, cell cycle, oocyte meiosis and homologous recombination. These results provide insights into the network of genes involved in heat-induced masculinization, and improve our understanding the molecular mechanisms of vertebrate sex determination.
2022-06-21 | GSE201748 | GEO
Project description:Cryptobranchid sex determination
Project description:Purpose: In this study we employed unbiased, genome-wide techniques to identify regulatory elements during murine sex determination. Methods: We performed ATAC-seq on 60K FACS-purified XX and XY gonadal cells before and after sex determination to map nucleosome depleted regions (NDRs) indicative of regulatory elements. To determine whether these are active enhancers, we performed ChIP-seq for H3K27ac, a histone modification that marks active enhancers in both sexes and time points. Transient transgenics was performed on select enhancers to determine whether they are functional in gonads during the sex determination stage. Results: We have produced a genome wide map of potential regulatory elements and active enhancers during the process of murine sex determination. Furthermore, we validated the power of our dataset by identifying a novel enhancer downstream of Bmp2, a female-specific gene. Conclusions: This work supplies a powerful resource for identifying chromatin regulatory elements active during mammalian sex determination.