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EIF5A couples translational control with transcriptional reprogramming through chromocenter reorganization during spermiogenesis [ATAC-Seq]

ABSTRACT: Translation initiation factor eIF5A facilitates protein synthesis and impacts diverse biological processes, yet its role in transcriptional regulation is poorly understood. Here we find eIF5A highly expressed in diverse spermatogenic cell types. Conditional knockout of Eif5a (SKO) causes complete infertility in male mice due to round spermatid arrest. Interestingly, eIF5A deletion severely compromises chromocenter integrity in round spermatids. Proteomic profiling reveals widespread dysregulation in eIF5A-deficient round spermatids, downregulated proteins are enriched for chromatin-associated functions, likely contributing to chromocenter dysfunction. Notably, ATAC-seq analysis shows increased chromatin accessibility upon eIF5A depletion, accompanied by transcriptional dysregulation of genes critical for acrosome and manchette formation. Our data underscore that eIF5A not only regulates the translation of chromatin-organizing proteins required for chromocenter stability but also influences transcriptional regulation by modulating chromatin landscape. These findings illuminate a novel, germ cell-specific pathway coupling translational control and transcriptional regulation via chromatin reorganization.

ORGANISM(S): Mus musculus

PROVIDER: GSE302914 | GEO | 2026/01/01

REPOSITORIES: GEO

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EIF5A couples translational control with transcriptional reprogramming through chromocenter reorganization during spermiogenesis [RNA-Seq]

Project description:Translation initiation factor eIF5A facilitates protein synthesis and impacts diverse biological processes, yet its role in transcriptional regulation is poorly understood. Here we find eIF5A highly expressed in diverse spermatogenic cell types. Conditional knockout of Eif5a (SKO) causes complete infertility in male mice due to round spermatid arrest. Interestingly, eIF5A deletion severely compromises chromocenter integrity in round spermatids. Proteomic profiling reveals widespread dysregulation in eIF5A-deficient round spermatids, downregulated proteins are enriched for chromatin-associated functions, likely contributing to chromocenter dysfunction. Notably, ATAC-seq analysis shows increased chromatin accessibility upon eIF5A depletion, accompanied by transcriptional dysregulation of genes critical for acrosome and manchette formation. Our data underscore that eIF5A not only regulates the translation of chromatin-organizing proteins required for chromocenter stability but also influences transcriptional regulation by modulating chromatin landscape. These findings illuminate a novel, germ cell-specific pathway coupling translational control and transcriptional regulation via chromatin reorganization.

2026-01-01 | GSE302912 | GEO

EIF5A couples translational control with transcriptional reprogramming through chromocenter reorganization during spermiogenesis [Ribo-Seq]

2026-01-01 | GSE302913 | GEO

BRD4 dynamics reveal novel acrosome-dependent chromatin reorganization during post-meiotic mammalian sperm development

Project description:During the post-meiotic phase of spermatogenesis, transcription is progressively repressed as the nuclei of haploid spermatids are compacted through a dramatic chromatin reorganization involving hyper-acetylation and replacement of most histones with sperm-specific protamines. Although BRDT has been shown to function in transcription as well as histone removal in post-meiotic spermatids, it is unknown whether other BET family proteins play a role. Immunofluorescence of mouse testes revealed BRD4 in a complete ring around the nuclei of spermatids containing hyper-acetylated histones. The BRD4 ring lies directly adjacent to the acroplaxome, or the cytoskeletal base of the acrosome, and does not form in acrosomal mutant mice. ChIP sequencing in round spermatids revealed enrichment of BRD4 and acetylated histone H3 and H4 at the promoters of active genes. GO Term analysis showed that BRD4 and BRDT bind to distinct subsets of spermatogenesis-specific genes. Association of BRD4 with Cyclin T1 decreases as spermatogenesis progresses despite a persistence of association with acetylated H4. Moreover, acetylated histones are removed from the condensing spermatid nucleus in a wave following the progressing acrosome. These data provide evidence for an interesting mechanism in which BRD4 and perhaps acetylated histones are removed from the spermatid genome via the progressing acrosome as transcription is repressed. Single replicates each of Brd4, H3K9me3, H3K9ac, H4K5ac, H4K8ac, H4K12ac, H4K16ac, H4Kac (pan-acetyl antibody), and input in mouse round spermatid cells; input is used to control for local sonication efficiency bias.

2015-03-06 | E-GEOD-56526 | biostudies-arrayexpress

BRD4 dynamics reveal novel acrosome-dependent chromatin reorganization during post-meiotic mammalian sperm development

2015-03-06 | GSE56526 | GEO

EIF5A couples translational control with transcriptional reprogramming through chromocenter reorganization during spermiogenesis [RNA-Seq]

Project description:EIF5A couples translational control with transcriptional reprogramming through chromocenter reorganization during spermiogenesis [RNA-Seq]

| PRJNA1292809 | ENA

EIF5A couples translational control with transcriptional reprogramming through chromocenter reorganization during spermiogenesis [Ribo-Seq]

Project description:EIF5A couples translational control with transcriptional reprogramming through chromocenter reorganization during spermiogenesis [Ribo-Seq]

| PRJNA1292810 | ENA

EIF5A couples translational control with transcriptional reprogramming through chromocenter reorganization during spermiogenesis [ATAC-Seq]

Project description:EIF5A couples translational control with transcriptional reprogramming through chromocenter reorganization during spermiogenesis [ATAC-Seq]

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Expression data from purified control and BrdtΔBD1 round spermatids.

Project description:Brdt is a testis specific member of a family of chromatin interacting proteins. All of the family members have been shown to regulate transcription. Brdt is highly expressed in round spermatids, and may play a role in transcriptional regulation in these cells. We investigated transcriptional changes in mutant round spermatids that were homozygous for a mutation in which the first bromodomain of Brdt was removed. Round spermatids were purified from seven adult animals of each genotype for each Affymetrix microarray. Purity of round spermatids was assessed by propidium iodide staining.

2011-10-20 | E-GEOD-33132 | biostudies-arrayexpress

Expression data from purified control and BrdtΔBD1 round spermatids.

2011-10-21 | GSE33132 | GEO

Paternally inherited H3K27me3 affects chromatin accessibility in mouse embryos produced by round spermatid injection

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

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