Genome-wide changes in chromatin accessibility in myoblasts lacking Daxx [ATAC-Seq]
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PROVIDER: PRJNA1162008 | ENA |
REPOSITORIES: ENA
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Project description:DAXX, a H3.3 histone chaperone known for its role in heterochromatin maintenance, has been understudied in the context of gene expression regulation. In this study, we generated Daxx knockout myogenic cells and observed a significant loss of myogenic markers expression and impaired differentiation. Transcriptome analysis revealed broad dysregulations in Daxx KO cells, including loss of myogenic identity and a concurrent upregulation of genes involved in DNA replication and telomere maintenance. Chromatin immunoprecipitation followed by sequencing demonstrated a marked reduction in H3.3 deposition, particularly in intronic and intergenic regions. Further analysis indicated that loss of DAXX leads to decreased H3K27ac at myogenic loci and a shift in repressive histone marks, which led to impaired gene expression. Intriguingly, double knockout of Daxx and Hira resulted in distinct transcriptomic alterations, demonstrating that DAXX and HIRA have both overlapping and unique roles in H3.3 incorporation. Our work also suggests the presence of additional histone chaperone complexes in maintaining chromatin integrity in myoblasts. Our findings establish DAXX as a critical regulator of myogenic gene expression and muscle cell identity through a distinct mechanism from that of HIRA and highlighted an unanticipated plasticity in the deposition loci for DAXX and HIRA in myoblasts.
2025-07-02 | GSE277345 | GEO
Project description:DAXX, a H3.3 histone chaperone known for its role in heterochromatin maintenance, has been understudied in the context of gene expression regulation. In this study, we generated Daxx knockout myogenic cells and observed a significant loss of myogenic markers expression and impaired differentiation. Transcriptome analysis revealed broad dysregulations in Daxx KO cells, including loss of myogenic identity and a concurrent upregulation of genes involved in DNA replication and telomere maintenance. Chromatin immunoprecipitation followed by sequencing demonstrated a marked reduction in H3.3 deposition, particularly in intronic and intergenic regions. Further analysis indicated that loss of DAXX leads to decreased H3K27ac at myogenic loci and a shift in repressive histone marks, which led to impaired gene expression. Intriguingly, double knockout of Daxx and Hira resulted in distinct transcriptomic alterations, demonstrating that DAXX and HIRA have both overlapping and unique roles in H3.3 incorporation. Our work also suggests the presence of additional histone chaperone complexes in maintaining chromatin integrity in myoblasts. Our findings establish DAXX as a critical regulator of myogenic gene expression and muscle cell identity through a distinct mechanism from that of HIRA and highlighted an unanticipated plasticity in the deposition loci for DAXX and HIRA in myoblasts.
2025-07-02 | GSE277346 | GEO
Project description:Genome-wide chromatin state in myoblasts lacking Daxx [ChIP-Seq]
| PRJNA1162006 | ENA
Project description:Genome-wide changes in chromatin accessibility in myoblasts lacking Hira [ATAC-seq]
| PRJNA675384 | ENA
Project description:DAXX, a H3.3 histone chaperone known for its role in heterochromatin maintenance, has been understudied in the context of gene expression regulation. In this study, we generated Daxx knockout myogenic cells and observed a significant loss of myogenic markers expression and impaired differentiation. Transcriptome analysis revealed broad dysregulations in Daxx KO cells, including loss of myogenic identity and a concurrent upregulation of genes involved in DNA replication and telomere maintenance. Chromatin immunoprecipitation followed by sequencing demonstrated a marked reduction in H3.3 deposition, particularly in intronic and intergenic regions. Further analysis indicated that loss of DAXX leads to decreased H3K27ac at myogenic loci and a shift in repressive histone marks, which led to impaired gene expression. Intriguingly, double knockout of Daxx and Hira resulted in distinct transcriptomic alterations, demonstrating that DAXX and HIRA have both overlapping and unique roles in H3.3 incorporation. Our work also suggests the presence of additional histone chaperone complexes in maintaining chromatin integrity in myoblasts. Our findings establish DAXX as a critical regulator of myogenic gene expression and muscle cell identity through a distinct mechanism from that of HIRA and highlighted an unanticipated plasticity in the deposition loci for DAXX and HIRA in myoblasts.
2025-07-02 | GSE277347 | GEO
Project description:Analysis of the transcriptomic changes of myoblasts lacking Daxx or both Daxx and Hira histone chaperones
| PRJNA1162005 | ENA
Project description:ATAC-seq, ChIP-seq and RNA-seq studies in myoblasts lacking Hira
| PRJNA675381 | ENA
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 deposition of these chromatin modifications is still incompletely understood. Here, we performed a genome-wide sgRNA screen for genes involved in ERV silencing and identified the GHKL ATPase protein Morc3 as top scoring hit. Morc3 knock-out cells display de-repression, reduced H3K9me3 and increased chromatin accessibility of distinct ERV classes. We found that the GHKL ATPase domain of Morc3 is critical for ERV silencing, since mutants which cannot bind ATP, or which are defective in ATP hydrolysis cannot rescue the Morc3 ko phenotype. Proteomic analysis revealed that Morc3 mutant protein which cannot bind ATP fails to interact with the H3.3 chaperone Daxx. This interaction depends on Morc3 sumoylation, as Daxx lacking the SUMO interaction domain shows reduced association with Morc3. Notably, in Morc3 ko cells, we observed strongly reduced H3.3 on Morc3 binding sites. Thus, our data demonstrate Morc3 as critical regulator of Daxx-mediated H3.3 incorporation into ERV regions.
2021-09-07 | GSE159932 | GEO
Project description:DAXX and ATRX are tumor suppressor proteins that form a complex with histone H3.3 chaperone and are frequently mutated in cancers with the alternative lengthening of telomeres (ALT), such as pediatric glioblastoma. Rapid loss of function of either DAXX or ATRX are not by themselves sufficient to induce the ALT phenotype. However, cells lacking DAXX or ATRX can be readily selected for ALT-like features. Here, we show that a key feature of ALT selected DAXX and ATRX null glioblastoma cells is the attenuation of p53 function. RNA-seq analysis of DAXX or ATRX null U87 glioblastoma cells with ALT-like features revealed that p53 pathway is among perturbed. ALT-selected DAXX and ATRX-null cells had aberrant response to DNA damaging agent etoposide. Both DAXX and ATRX-null ALT cells showed a loss of p53 binding at a subset of response elements. Complementation of DAXX null cells with wt DAXX rescued p53 binding and transcription, while the tumor associated mutation L130R, that disrupts ATRX binding, was incapable of rescuing p53 chromatin binding. We show that histone H3.3 binding is reduced in DAXX-null cells especially at subtelomeric p53 binding sites and telomere repeats. These findings indicate that DAXX and ATRX function to enable p53 chromatin binding through modulation of histone H3.3 binding, especially at sub-telomeric sites.
2022-07-19 | GSE207046 | GEO
Project description:Genome-wide chromatin state in myoblasts lacking Hira [ChIP-seq]
| PRJNA675385 | ENA