DAXX interacts with histone acylation in gene regulation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE169229 | GEO | 2025/09/06
REPOSITORIES: GEO
Similar Datasets
Project description:A multitude of histone chaperones are required to support histones from their biosynthesis until DNA deposition. They cooperate through the formation of histone co-chaperone complexes, but the crosstalk between nucleosome assembly pathways remains enigmatic. Using exploratory interactomics, we define the interplay between histone H3–H4 chaperones in the histone chaperone network. We identify several novel histone dependent complexes and predict the structure of the ASF1 and SPT2 co-chaperone complex, expanding the role of ASF1 in histone dynamics. We show that DAXX provides a unique functionality to the histone chaperone network, recruiting histone methyltransferases to promote H3K9me3 catalysis on new histone H3.3–H4 prior to deposition onto DNA. Hereby, DAXX provides a molecular mechanism for de novo H3K9me3 deposition and heterochromatin assembly. Collectively, our findings provide a framework for understanding how cells orchestrate histone supply and employ targeted deposition of modified histones to underpin specialized chromatin states.
2023-03-02 | PXD038263 | Pride
Project description:A multitude of histone chaperones are required to support histones from their biosynthesis until DNA deposition. They cooperate through the formation of histone co-chaperone complexes, but the crosstalk between nucleosome assembly pathways remains enigmatic. Using exploratory interactomics, we define the interplay between histone H3–H4 chaperones in the histone chaperone network. We identify several novel histone dependent complexes and predict the structure of the ASF1 and SPT2 co-chaperone complex, expanding the role of ASF1 in histone dynamics. We show that DAXX provides a unique functionality to the histone chaperone network, recruiting histone methyltransferases to promote H3K9me3 catalysis on new histone H3.3–H4 prior to deposition onto DNA. Hereby, DAXX provides a molecular mechanism for de novo H3K9me3 deposition and heterochromatin assembly. Collectively, our findings provide a framework for understanding how cells orchestrate histone supply and employ targeted deposition of modified histones to underpin specialized chromatin states.
2023-03-02 | PXD034888 | Pride
Project description:DAXX interacts with histone acylation in gene regulation
| PRJNA715759 | ENA
Project description:A multitude of histone chaperones is required to protect histones from their biosynthesis to DNA deposition. They cooperate through the formation of co-chaperone complexes, but the crosstalk between nucleosome assembly pathways is unclear. Using explorative interactomics approaches, we map the organization of the histone H3-H4 chaperones network and define the interplay between histone chaperones systems. We identify and validate a panel of novel histone (PTM) dependent complexes. We show DAXX acts separately from the rest of the network, recruiting heterochromatin factors and promoting lysine 9 tri-methylated new histone H3.3 prior to deposition onto DNA. With its functionality, DAXX provides a molecular mechanism for de novo heterochromatin assembly.
2023-03-06 | PXD034924 | Pride
Project description:Objective: Daxx is a protein with multiple functions and is essential for embryonic development. Daxx knockout embryos fail to develop properly and exhibit lethal phenotype around E6.5. One of the important functions is as a histone chaperone for the histone H3 variant, H3.3. Daxx interacts with Atrx to form a protein complex that deposits H3.3 into heterochromatic regions of the genome, including centromeres, telomeres and repeat loci. Here, we investigated how histone chaperone function of Daxx contributes to the embryonic development. Methods: We developed two Daxx mutant alleles in the mouse germline which abolish the interactions between Daxx and Atrx (DaxxY130A), Daxx and H3.3 (DaxxS226A). We set up mating between either heterozygous DaxxY130A or heterozygous DaxxS226A individually and looked for the viability of homozygous mutants at different development stages. We also performed bulk RNA-seq on tissues from the two mutant embryos and analyzed the changes in gene expression and transposable elements (TE). Results: We found that the interaction between Daxx and Atrx is dispensable for viability in both the pre- and post-natal setting as homozygous Daxx-Y130A mutants are both viable and fertile. The loss of the Atrx interaction, however, does cause dysregulated expression of both endogenous retroviruses and nearby protein coding genes. On the contrary, the interaction between Daxx and H3.3 is not required for embryonic development but is essential for postnatal viability. Transcriptome analysis of embryonic tissues demonstrates that this interaction is important for silencing endogenous retroviruses and for maintaining proper hematopoiesis. Conclusions: The histone chaperone function of Daxx is dispensable for embryonic development but important for hematopoiesis, which is independent of the interaction with Atrx. Moreover, both the interactions with Atrx and with H3.3 is important for regulation of ERV expression. Overall, these results clearly demonstrate that Daxx and H3.3 have both Atrx-dependent and independent functions, advancing our understanding of this epigenetic regulatory complex.
2023-05-01 | GSE223912 | 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 | GSE277347 | GEO
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: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:<p>Many tumors maintain chromosome ends through a telomerase-independent, homologous recombination based mechanism called alternative lengthening of telomeres (ALT). While ALT occurs in only a subset of tumors, it is strongly associated with mutations in the genes encoding components of the histone H3.3 chaperone complex, ATRX and DAXX. To date the mechanistic role of ATRX and particularly DAXX mutations in potentiating ALT remains poorly understood. We identify an osteosarcoma cell line, G292, with a unique chromosomal translocation resulting in loss of DAXX function, while retaining functional ATRX. Using this distinctive resource, we demonstrate that introduction of wild type DAXX suppresses the ALT phenotype and restores localization of the ATRX/DAXX complex to PML bodies. This provides the first direct molecular evidence that ongoing DAXX deficiency is essential for maintenance of the ALT phenotype and highlights the potential for therapeutic targeting of this oncogenic pathway.</p>
| phs001495 | dbGaP
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