Transcription Factor RFX2 Is a Key Regulator of Mouse Spermiogenesis
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE74961 | GEO | 2017/02/09
SECONDARY ACCESSION(S): PRJNA302160
REPOSITORIES: GEO
Similar Datasets
Project description:Tadpole-shaped sperm is formed from round spermatid by spermiogenesis, a process with dramatic morphological changes in the final stage of spermatogenesis in testis. Protein phosphorylation, as one of the most important post-translational modifications, can regulate spermiogenesis, however, there is a lack of systemic analysis for phosphorylation events in this process. By large-scale phosphoproteome profiling using IMAC and TiO2 enrichment, we identified 18,980 phosphorylation sites in 4,628 phosphoproteins in mouse purified spermatids undergoing spermiogenesis. The identified phosphoproteins were significantly enriched in RNA transport, cell-cell adhesion, centrosome, microtubule and cilliogenesis. Further characterization of the kinase substrate relationship network demonstrated enrichment of phosphorylation substrates were related to the regulation of spermiogenesis. This global protein phosphorylation landscape of spermiogenesis showed wide phosphoregulation of diverse processes during spermiogenesis and could help further characterization of the process of sperm generation.
2019-03-29 | PXD011890 | Pride
Project description:Actin-related proteins (Arp) are classified according to their similarity to actin and are involved in diverse cellular processes. ACTL7B is a testis-specific Arp and highly conserved in rodents and primates. ACTL7B is specifically expressed in round and elongating spermatids during spermiogenesis. Here, we have generated an Actl7b-null allele in mice to unravel the role of ACTL7B in sperm formation. Male mice homozygous for the Actl7b-null allele (Actl7b-/-) were infertile, while heterozygous males (Actl7b+/-) were fertile. Severe spermatid defects such as detached acrosomes, disrupted membranes and failed elongation of the axoneme start to appear at spermiogenesis step 9 in Actl7b-/- mice, finally resulting in spermatogenic arrest. Abnormal spermatids, were degraded. Co-immunoprecipitation experiments identified interaction between ACTL7B and the LC8 dynein light chains DYNLL1 and DYNLL2, which are first detected in step 9 spermatids and mislocalized when ACTL7B is absent. Our data unequivocally establishes that mutations in ACTL7B are directly related to male infertility, pressing for additional research in men.
2023-10-19 | PXD038920 | Pride
Project description:Purpose: This study was carried out to determine the consequences of the Rfx2-/- genotype on spermatogenesis in the mouse Methods: DNA was extracted from decapsulated testes of 21 day old mice. ChIP sequencing was used to determine the binding sites of RFX2. Results: ChIP-Seq analysis identified ~880 binding sites of RFX2 near TSS. Conclusion: Spermatogenesis undergoes complete arrest just prior to the end of the round spermatid period of sperm development in mutant mice. Sequencing results showed that approximately 105 genes were downregulated 2 fold or more in the testes of mutant mice. Comparison of similar studies of targeted mutations in genes for other transcription factor demonstrate that Rfx2 has a large and nearly unique set of genes that depend on it directly or indirectly. A large number of downregulated genes are identified with cilia function.
2015-11-02 | GSE68282 | GEO
Project description:Purpose: This study was carried out to determine the consequences of the Rfx2-/- genotype on spermatogenesis in the mouse Methods: DNA was extracted from decapsulated testes of 21 day old mice. ChIP sequencing was used to determine the binding sites of RFX2. Results: ChIP-Seq analysis identified ~880 binding sites of RFX2 near TSS. Conclusion: Spermatogenesis undergoes complete arrest just prior to the end of the round spermatid period of sperm development in mutant mice. Sequencing results showed that approximately 105 genes were downregulated 2 fold or more in the testes of mutant mice. Comparison of similar studies of targeted mutations in genes for other transcription factor demonstrate that Rfx2 has a large and nearly unique set of genes that depend on it directly or indirectly. A large number of downregulated genes are identified with cilia function. Testicular RFX2 binding sites were determined by deep sequencing using testes from 2 independentWT mice
2015-11-02 | E-GEOD-68282 | biostudies-arrayexpress
Project description:Round spermatid injection (ROSI) results in a lower birth rate than intracytoplasmic sperm injection, which has hampered its clinical application. Inefficient development of ROSI embryos has been attributed to epigenetic abnormalities. However, the chromatin-based mechanism that underpins the low birth rate in ROSI remains to be determined. Here, we show that a repressive histone mark H3K27me3 persists from mouse round spermatids into zygotes in ROSI and that round spermatid-derived H3K27me3 is associated with less accessible chromatin and impaired gene expression in ROSI embryos. These loci are initially marked by H3K27me3 but undergo histone modification remodelling in spermiogenesis, resulting in reduced H3K27me3 in normal spermatozoa. Therefore, the absence of the epigenetic remodelling, presumably mediated by histone turnover during spermiogenesis, leads to dysregulation of chromatin accessibility and transcription in ROSI embryos. Thus, our results unveil a molecular logic, in which chromatin states in round spermatids impinge on chromatin accessibility and transcription in ROSI embryos, highlighting the importance of epigenetic remodelling during spermiogenesis in successful reproduction.
2022-08-22 | GSE196859 | GEO
Project description:DEGs in the round and elongating spermatids between the WT and Carm1-null testis.
2018-05-30 | GSE107984 | GEO
Project description:Purpose: This study was carried out to determine the consequences of the Rfx2-/- genotype on spermatogenesis in the mouse Methods: RNA was extracted from decapsulated testes of 21 day old mixed background mice of either genotype. Deep sequencing was used to determine quantitative expression of the genomes from independent replicates of each genotype Results: RNA-Seq analysis identified some 105 genes that are down regulated at least 2-fold in Rfx2-/- testes, with ~50 being reduced at least 10-fold Conclusion: Spermatogenesis undergoes complete arrest just prior to the end of the round spermatid period of sperm development in mutant mice. Sequencing results showed that approximately 105 genes were downregulated 2 fold or more in the testes of mutant mice. Comparison of similar studies of targeted mutations in genes for other transcription factor demonstrate that Rfx2 has a large and nearly unique set of genes that depend on it directly or indirectly. A large number of downregulated genes are identified with cilia function.
2015-11-02 | GSE68284 | GEO
Project description:Purpose: This study was carried out to determine the consequences of the Rfx2-/- genotype on spermatogenesis in the mouse Methods: RNA was extracted from decapsulated testes of 29-30 day old mixed background mice of either genotype. Deep sequencing was used to determine quantitative expression of the genomes from independent replicates of each genotype Results: RNA-Seq analysis identified some 640 genes that are down regulated at least 2-fold in Rfx2-/- testes, with ~150 being reduced at least 10-fold Conclusion: Spermatogenesis undergoes complete arrest just prior to the end of the round spermatid period of sperm development in mutant mice. Sequencing results showed that approximately 640 genes were downregulated 2 fold or more in the testes of mutant mice. Comparison of similar studies of targeted mutations in genes for other transcription factor demonstrate that Rfx2 has a large and nearly unique set of genes that depend on it directly or indirectly. A large number of downregulated genes are identified with cilia function.
2015-11-02 | GSE68283 | GEO
Project description:Spermatogenesis is a recurring differentiation process that results in the production of male gametes within the testes. During this process, spermatogonial stem cells differentiate to form spermatocytes, which undergo two rounds of meiotic division to form haploid spermatids. Throughout spermiogenesis, round spermatids elongate to form mature sperm. To profile changes in chromatin marks between spermatocytes and spermatids, we generated CUT&RUN data of H3K4me3, H3K27ac and H3K9me3 marks in sorted spermatocytes and spermatids.
2019-01-25 | E-MTAB-6932 | biostudies-arrayexpress
Project description:Nonobstructive azoospermia (NOA) is one of the most severe forms of male infertility, characterized by the absence of spermatozoa in the ejaculate. The etiology and genetic mechanism(s) of this disease remain largely unclear. Using Sanger sequence, we identified 12 heterozygous missense mutations and 2 heterozygous nonsense mutations in the HIPK4, encoding a serine/threonine kinase. Moreover, K490* mutant cause HIPK4 unstable in 293T cells. In accord with these findings, we observed that homozygous Hipk4-/- male mice were infertility owing to malformed and immotile spermatozoa, which are characterized by a deformed nucleus and a detached acrosome. Furthermore, we performed a phosphoproteomic analysis of testis from Hipk4 wild type and knockout mice, revealing multiple targets regulated by Hipk4 during spermiogenesis. Notably, manchette-associated protein Rimbp3 has multiple phosphorylation sites regulated by Hipk4. Moreover, Hipk4 and Rimbp3 deficiency mice display several common phenotypes, in particular with regard to the ectopic positioning of the manchette within spermatids, a presumed cause of sperm head deformities. Thus, Hipk4 might regulate manchette function through phosphorylation of Rimbp3, thereby playing essential role for sperm head formation and male fertility.
2022-08-02 | PXD019303 | Pride