Similar Datasets
Project description:During spermatogenesis, extensive chromatin remodeling and histone replacement reshape the male germline epigenome. While HIRA is known to mediate transcription-coupled incorporation of histone variant H3.3, we identify DAXX as a key histone chaperone directing genome-wide, transcription-dependent replacement of H3.4 (H3T) with H3.3 on autosomes during male meiosis. Simultaneously, DAXX also directs transcription-independent H3.4-to-H3.3 replacement on the sex chromosomes during meiotic sex chromosome inactivation (MSCI). These distinct, chromosome-specific modes of DAXX-mediated H3.3 deposition are essential for epigenomic integrity in the male germline. Loss of DAXX disrupts this process, leading to widespread transcriptional dysregulation in haploid round spermatids and male infertility.
2026-01-13 | GSE308004 | GEO
Project description:During spermatogenesis, extensive chromatin remodeling and histone replacement reshape the male germline epigenome. While HIRA is known to mediate transcription-coupled incorporation of histone variant H3.3, we identify DAXX as a key histone chaperone directing genome-wide, transcription-dependent replacement of H3.4 (H3T) with H3.3 on autosomes during male meiosis. Simultaneously, DAXX also directs transcription-independent H3.4-to-H3.3 replacement on the sex chromosomes during meiotic sex chromosome inactivation (MSCI). These distinct, chromosome-specific modes of DAXX-mediated H3.3 deposition are essential for epigenomic integrity in the male germline. Loss of DAXX disrupts this process, leading to widespread transcriptional dysregulation in haploid round spermatids and male infertility.
2026-01-13 | GSE308003 | GEO
Project description:DAXX Directs H3.4-to-H3.3 Histone Replacement During Spermatogenesis
| PRJNA1331851 | ENA
Project description:DAXX Directs H3.4-to-H3.3 Histone Replacement During Spermatogenesis [Cut & Run]
| PRJNA1328499 | ENA
Project description:DAXX Directs H3.4-to-H3.3 Histone Replacement During Spermatogenesis [RNA-Seq]
| PRJNA1328501 | ENA
Project description:The histone variant H3.3 is involved in diverse biological processes, including development, transcriptional memory and transcriptional reprogramming, as well as diseases, including most notably malignant brain tumors. Recently, we developed a knockout mouse model for the H3f3b gene, one of two genes encoding H3.3. Here, we show that targeted disruption of H3f3b results in a number of phenotypic abnormalities, including a reduction in H3.3 histone levels, leading to male infertility, as well as abnormal sperm and testes morphology. Additionally, null germ cell populations at specific stages in spermatogenesis, in particular spermatocytes and spermatogonia, exhibited increased rates of apoptosis. Disruption of H3f3b also altered histone post-translational modifications and gene expression in the testes, with the most prominent changes occurring at genes involved in spermatogenesis. Finally, H3f3b null testes also exhibited abnormal germ cell chromatin reorganization and reduced protamine incorporation. Taken together, our studies indicate a major role for H3.3 in spermatogenesis through regulation of chromatin dynamics.
| S-EPMC4197731 | biostudies-literature
Project description:Histone chaperones represent a structurally and functionally diverse family of histone-binding proteins that prevent promiscuous interactions of histones before their assembly into chromatin. DAXX is a metazoan histone chaperone specific to the evolutionarily conserved histone variant H3.3. Here we report the crystal structures of the DAXX histone-binding domain with a histone H3.3-H4 dimer, including mutants within DAXX and H3.3, together with in vitro and in vivo functional studies that elucidate the principles underlying H3.3 recognition specificity. Occupying 40% of the histone surface-accessible area, DAXX wraps around the H3.3-H4 dimer, with complex formation accompanied by structural transitions in the H3.3-H4 histone fold. DAXX uses an extended α-helical conformation to compete with major inter-histone, DNA and ASF1 interaction sites. Our structural studies identify recognition elements that read out H3.3-specific residues, and functional studies address the contributions of Gly 90 in H3.3 and Glu 225 in DAXX to chaperone-mediated H3.3 variant recognition specificity.
| S-EPMC4056191 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-09-07 | GSE159936 | GEO
Project description:Endogenous retroviruses (ERVs) comprise a significant portion of mammalian genomes. Although specific ERV loci feature regulatory roles for host gene expression, most ERV integrations are transcriptionally repressed by Setdb1-mediated H3K9me3 and DNA methylation. However, the protein network which regulates the deposition of these chromatin modifications is still incompletely understood. Here, we perform a genome-wide single guide RNA (sgRNA) screen for genes involved in ERV silencing and identify the GHKL ATPase protein Morc3 as a top-scoring hit. Morc3 knock-out (ko) cells display de-repression, reduced H3K9me3, and increased chromatin accessibility of distinct ERV families. We find that the Morc3 ATPase cycle and Morc3 SUMOylation are important for ERV chromatin regulation. Proteomic analyses reveal that Morc3 mutant proteins fail to interact with the histone H3.3 chaperone Daxx. This interaction depends on Morc3 SUMOylation and Daxx SUMO binding. Notably, in Morc3 ko cells, we observe strongly reduced histone H3.3 on Morc3 binding sites. Thus, our data demonstrate Morc3 as a critical regulator of Daxx-mediated histone H3.3 incorporation to ERV regions.
| S-EPMC8516933 | biostudies-literature
Project description:The incorporation of the histone H3 variant, H3.3, into chromatin by the H3.3-specific chaperone DAXX and the ATP-dependent chromatin remodeling factor ATRX is a critical mechanism for silencing repetitive DNA. DAXX and ATRX are also components of promyelocytic nuclear bodies (PML-NBs), which have been identified as sites of H3.3 chromatin assembly. Here, we use a transgene array that can be visualized in single living cells to investigate the mechanisms that recruit PML-NB proteins (i.e. PML, DAXX, ATRX, and SUMO-1, SUMO-2 and SUMO-3) to heterochromatin and their functions in H3.3 chromatin assembly. We show that DAXX and PML are recruited to the array through distinct SUMOylation-dependent mechanisms. Additionally, PML is recruited during S phase and its depletion increases H3.3 deposition. Since this effect is abrogated when PML and DAXX are co-depleted, it is likely that PML represses DAXX-mediated H3.3 chromatin assembly. Taken together, these results suggest that, at heterochromatin, PML-NBs coordinate H3.3 chromatin assembly with DNA replication, which has important implications for understanding how transcriptional silencing is established and maintained.
| S-EPMC6451418 | biostudies-literature