Analysis of the transcriptomic changes of myoblasts lacking Daxx or both Daxx and Hira histone chaperones
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PROVIDER: PRJNA1162005 | 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 | GSE277347 | 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: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:The centromere specific histone H3 variant CENP-A/CENH3 specifies where the kinetochore is formed in most eukaryotes. Despite tight regulation of CENP-A levels in normal cells, overexpression of CENP-A is a feature shared by various types of solid tumors and results in its mislocalization to non-centromeric DNA. How CENP-A is assembled ectopically and the consequences of this mislocalization remain topics of high interest. Here, we report that in human colon cancer cells, the H3.3 chaperones HIRA and DAXX promote ectopic CENP-A deposition. Moreover, the correct balance between levels of the centromeric chaperone HJURP and CENP-A is essential to preclude ectopic assembly by H3.3 chaperones. In addition, we find that ectopic localization can recruit kinetochore components, and correlates with mitotic defects and DNA damage in G1 phase. Finally, CENP-A occupancy at the 8q24 locus is also correlated with amplification and overexpression of the MYC gene within that locus. Overall, these data provide insights into the causes and consequences of histone variant mislocalization in human cancer cells.
2018-10-10 | GSE120230 | GEO
Project description:Genome-wide chromatin state in myoblasts lacking Daxx [ChIP-Seq]
| PRJNA1162006 | ENA
Project description:Genome-wide chromatin state in myoblasts lacking Hira [ChIP-seq]
| PRJNA675385 | ENA
Project description:HJURP antagonizes CENP-A mislocalization driven by the H3.3 chaperones HIRA and DAXX
| PRJNA492248 | ENA
Project description:Histone chaperones prevent promiscuous histone interactions before chromatin assembly. They guarantee faithful deposition of canonical histones and functionally specialized histone variants into chromatin in a spatial- and temporally-restricted manner. Here, we identify the binding partners of the primate-specific and H3.3-related histone variant H3.Y using several quantitative mass spectrometry approaches, and biochemical and cell biological assays. We find the HIRA, but not the DAXX/ATRX, complex to specifically recognize H3.Y, explaining its presence in transcriptionally active euchromatic regions. Accordingly, H3.Y nucleosomes are enriched in the transcription-promoting FACT complex and depleted of repressive posttranslational histone modifications. H3.Y mutational gain-of-function analyses screens reveal an unexpected combinatorial amino acid sequence requirement for histone H3.3 interaction with DAXX but not HIRA, and for H3.3 recruitment to PML nuclear bodies. We demonstrate the importance and necessity of specific H3.3 core region and C-terminal amino acids in discriminating between distinct chaperone complexes. Further, ChIP-seq experiments reveal that in contrast to euchromatic HIRA-dependent deposition sites, human DAXX/ATRX-dependent regions of histone H3 variant incorporation are enriched in heterochromatic H3K9me3 and simple repeat sequences. These data demonstrate that H3.Y's unique amino acids allow a functional distinction between HIRA and DAXX binding and its consequent deposition into open chromatin.
2017-03-13 | GSE94034 | GEO
Project description:Analysis of the transcriptomic changes of myoblasts lacking Hira [RNA-seq]
| PRJNA675386 | ENA
Project description:Genome-wide changes in chromatin accessibility in myoblasts lacking Daxx [ATAC-Seq]
| PRJNA1162008 | ENA