Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide chromatin state in myoblasts lacking Daxx [ChIP-Seq]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE277346 | GEO | 2025/07/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Analysis of the transcriptomic changes of myoblasts lacking Daxx or both Daxx and Hira histone chaperones

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

Genome-wide changes in chromatin accessibility in myoblasts lacking Daxx [ATAC-Seq]

2025-07-02 | GSE277345 | GEO

H3.Y discriminates between HIRA and DAXX chaperone complexes and reveals unexpected insights into human DAXX-H3.3-H4 binding and deposition requirements

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

HIRA protects telomeres against R-loop-induced instability in ALT cancer cells [ATAC-seq]

Project description:Alterations to chromatin modifiers, such as the inactivating mutations in the ATRX-DAXX chromatin remodeling/histone H3.3 deposition complex, are implicated as drivers of the cancer-specific Alternative Lengthening of Telomeres (ALT) pathway. Prior studies revealed that HIRA adapts to compensate for ATRX-DAXX loss to sustain ALT cancer cell survival. However, the specific mechanisms underlying HIRA’s ability to rescue telomeres from the consequences of ATRX-DAXX loss remain unclear. Here, using ATAC-seq and CUT&RUN, we demonstrate that HIRA-mediated deposition of new H3.3 is essential to maintain chromatin accessibility and to prevent the detrimental accumulation of nucleosome-free single-stranded DNA (ssDNA) at telomeres in ATRX-deficient ALT cancer cells. We provide evidence that the timely deposition of new H3.3 by HIRA and interacting partners UBN1 and UBN2 is crucial to prevent unwarranted TERRA R-loop formation and transcription-replication conflicts (TRCs) at telomeres. Furthermore, we determined that the delivery of H3.3 to telomeric chromatin by HIRA may link the phosphorylation of an H3.3-specific amino acid, serine 31, by Chk1 with mechanisms that promote productive ALT. Therefore, these studies identify a role for HIRA-mediated histone H3.3 deposition in TERRA R-loop homeostasis that we propose is essential for ensuring the survival of ALT cancer cells where the ATRX-DAXX complex is activated.

2024-10-21 | GSE269268 | GEO

HIRA protects telomeres against R-loop-induced instability in ALT cancer cells [CUT&RUN]

2024-10-21 | GSE269261 | GEO

Genome-wide maps of chromatin state for HIRA, UBN1 and ASF1a

Project description:The HIRA chaperone complex, comprised of HIRA, UBN1 and CABIN1, collaborates with histone-binding protein ASF1a to incorporate histone variant H3.3 into chromatin in a DNA replication-independent manner. To better understand its function and mechanism, we integrated HIRA, UBN1, ASF1a and histone H3.3 ChIP-seq and gene expression analyses. Most HIRA-binding sites co-localize with UBN1, ASF1a and H3.3 at active promoters and active and weak/poised enhancers. At promoters, binding of HIRA/UBN1/ASF1a correlates with the level of gene expression. HIRA is required for deposition of histone H3.3 at its binding sites. There are marked differences in nucleosome and co-regulator composition at different classes of HIRA-bound regulatory site. Underscoring this, we report novel physical interactions between the HIRA complex and transcription factors, a chromatin insulator and an ATP-dependent chromatin-remodelling complex. Our results map the distribution of the HIRA chaperone across the chromatin landscape and point to different interacting partners at functionally distinct regulatory sites. Examination of 3 histone chaperone proteins in HeLa cells

2013-04-18 | E-GEOD-45024 | biostudies-arrayexpress

Genome-wide maps of chromatin state for H3.3 tagged cells

2013-04-18 | E-GEOD-45023 | biostudies-arrayexpress

Genome-wide changes in chromatin accessibility in myoblasts lacking Hira [ATAC-seq]

Project description:The epigenetic mechanisms coordinating the maintenance of adult cellular lineages and the inhibition of alternative cell fates are poorly understood. Here we show that targeted ablation of the histone chaperone HIRA in myogenic cells leads to extensive transcriptional modifications consistent with a major role in maintaining skeletal muscle cellular identity. Conditional ablation of HIRA in muscle stem cells of adult mice compromised their capacity to regenerate and self-renew, leading to tissue repair failure. Epigenetic analysis of Hira-deficient cells showed a drastic reduction of histone variant H3.3 deposition and H3K27ac modification at regulatory regions of muscle genes. By contrast, genes from alternative lineages were ectopically expressed in Hira-mutant cells via MLL1/MLL2-mediated increase of H3K4me3 mark at silent promoter regions. Therefore, HIRA sustains the epigenetic landscape governing muscle cell lineage identity via incorporation of H3.3 at muscle gene regulatory regions, while preventing the expression of alternative lineage genes.

2021-05-03 | GSE161053 | GEO

Analysis of the transcriptomic changes of activated satellite cells lacking Hira

2021-05-03 | GSE167911 | GEO

Analysis of the transcriptomic changes of myoblasts lacking Hira [RNA-seq]

2021-05-03 | GSE161055 | GEO