Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epigenetic reprogramming of the mesenchymal state by SUV39H1/H2 [ChIP-Seq]

ABSTRACT: Emergence of chemotherapy resistance is a major clinical challenge resulting in large number of deaths yearly. One mechanism involves epigenetic reprogramming through which cancer cells acquire mesenchymal (M) properties akin to cancer stem cells. How cells epigenetically establish resistance to chemotherapy is largely unknown. Here, we show that the two human lysine 9 histone H3 (H3K9) methyltransferase proteins (SUV39H1 and SUV39H2) play a central role in maintaining mesenchymal, chemotherapy resistant state in several cancer models. More importantly, a transient inhibition of these enzymes results in an epigenetic change, triggering a mesenchymal-to-epithelial transition and sensitizing these cells to chemotherapy. These data expand the functional repertoire of SUV39H family of proteins in eukaryotes and expose new therapeutic targets for neutralizing chemotherapy resistance in cancers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE206726 | GEO | 2025/06/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Epigenetic reprogramming of the mesenchymal state by SUV39H1/H2 [RNA-Seq]

Project description:Emergence of chemotherapy resistance is a major clinical challenge resulting in large number of deaths yearly. One mechanism involves epigenetic reprogramming through which cancer cells acquire mesenchymal (M) properties akin to cancer stem cells. How cells epigenetically establish resistance to chemotherapy is largely unknown. Here, we show that the two human lysine 9 histone H3 (H3K9) methyltransferase proteins (SUV39H1 and SUV39H2) play a central role in maintaining mesenchymal, chemotherapy resistant state in several cancer models. More importantly, a transient inhibition of these enzymes results in an epigenetic change, triggering a mesenchymal-to-epithelial transition and sensitizing these cells to chemotherapy. These data expand the functional repertoire of SUV39H family of proteins in eukaryotes and expose new therapeutic targets for neutralizing chemotherapy resistance in cancers.

2025-06-20 | GSE206727 | GEO

SUV39H1 Maintains Cancer Stem Cells in Glioblastoma [RNA-seq]

Project description:Glioblastoma (GBM) is the deadliest brain cancer, driven in part by GBM stem cells (GSCs) that contribute to therapeutic resistance and tumor recurrence. Effective targeting and elimination of GSCs hold promise for preventing GBM recurrence and achieving potential cures. In this study, we explored the role of the epigenetic regulator SUV39H1 in GSC maintenance and GBM progression. We observed that SUV39H1 is upregulated in GBM samples compared to normal brain tissues. Single-cell RNA-seq data indicated that SUV39H1 is preferentially expressed in GSCs relative to non-stem GBM cells, possibly due to super-enhancer-mediated transcriptional activation. Knockdown of SUV39H1 in patient-derived GSCs impaired their proliferation and stemness. RNA-seq analysis revealed that SUV39H1 regulates G2/M cell cycle progression, stem cell maintenance, and cell death pathways in GSCs. Integrated ATAC-seq (assay for transposase-accessible chromatin followed by sequencing) and RNA-seq analyses demonstrated that targeting SUV39H1 altered chromatin accessibility in key genes associated with these pathways. Treatment with chaetocin, a SUV39H1 inhibitor, mimicked the effects of SUV39H1 knockdown in GSCs and sensitized them to the GBM chemotherapy drug temozolomide (TMZ). In vivo studies using an intracranial patient-derived xenograft model showed that targeting SUV39H1 inhibited GSC-driven tumor formation in mice. Our findings identify SUV39H1 as a critical regulator of GSC maintenance and suggest that targeting SUV39H1 could disrupt GSCs and enhance the efficacy of existing chemotherapy, offering a promising strategy for improving GBM treatment outcomes.

2024-11-06 | GSE273012 | GEO

SUV39H1 Maintains Cancer Stem Cells in Glioblastoma [ATAC-seq]

2024-11-06 | GSE273013 | GEO

Epigenetic reprogramming of the mesenchymal state by SUV39H1/H2

Project description:Epigenetic reprogramming of the mesenchymal state by SUV39H1/H2

| PRJNA851821 | ENA

DNA hypomethylation promotes UHRF1- and SUV39H1/H2-dependent crosstalk between H3K18ub and H3K9me3 to reinforce heterochromatin states

Project description:Mono-ubiquitination of lysine 18 on histone H3 (H3K18ub), catalyzed by UHRF1, is a DNMT1 docking site that facilitates replication-coupled DNA methylation maintenance. Its functions beyond this are unknown. Here, we genomically map simultaneous increases in UHRF1-dependent H3K18ub and SUV39H1/H2-dependent H3K9me3 following DNMT1 inhibition. Mechanistically, transient accumulation of hemi-methylated DNA at CpG islands facilitates UHRF1 recruitment and E3 ligase activity towards H3K18. Notably, H3K18ub enhances SUV39H1/H2 methyltransferase activity and, in colon cancer cells, nucleates new H3K9me3 domains at CpG island promoters of DNA methylation-silenced tumor suppressor genes. Disrupting UHRF1 enzyme activity prevents H3K9me3 accumulation while promoting PRC2-dependent H3K27me3 as a tertiary layer of gene repression in these regions. In contrast, disrupting H3K18ub- dependent SUV39H1/H2 activity enhances the transcriptional activating and antiproliferative effects of DNMT1 inhibition. Collectively, these findings reveal roles for UHRF1 and H3K18ub in regulating a hierarchy of repressive histone methylation signaling and rationalize a combination strategy for epigenetic cancer therapy.

2024-12-03 | GSE256133 | GEO

DNA hypomethylation promotes UHRF1- and SUV39H1/H2-dependent crosstalk between H3K18ub and H3K9me3 to reinforce heterochromatin states

2024-12-03 | GSE256116 | GEO

DNA hypomethylation promotes UHRF1- and SUV39H1/H2-dependent crosstalk between H3K18ub and H3K9me3 to reinforce heterochromatin states

2024-12-03 | GSE256114 | GEO

RNA-seq profiles of DP thymocytes from control and Suv39h1/Suv39h2 double knockout mice

Project description:H3K9me3-dependent heterochromatin is critical for the silencing of repeat-rich pericentromeric regions and also has key roles in repressing lineage-inappropriate protein-coding genes for healthy cellular function. Here we investigate the transcriptomic effects of heterochromatin loss in primary immune cells deficient in both Suv39h1 and Suv39h2 (Suv39DKO), the major mammalian histone methyltransferase enzymes which catalyse heterochromatic H3K9me3 deposition.

2024-03-27 | GSE156296 | GEO

DNA hypomethylation promotes UHRF1- and SUV39H1/H2-dependent crosstalk between H3K18ub and H3K9me3 to reinforce heterochromatin states [EPIC]

Project description:Mono-ubiquitination of lysine 18 on histone H3 (H3K18ub), catalyzed by UHRF1, is a DNMT1 docking site that facilitates replication-coupled DNA methylation maintenance. Its functions beyond this are unknown. Here, we genomically map simultaneous increases in UHRF1-dependent H3K18ub and SUV39H1/H2-dependent H3K9me3 following DNMT1 inhibition. Mechanistically, transient accumulation of hemi-methylated DNA at CpG islands facilitates UHRF1 recruitment and E3 ligase activity towards H3K18. Notably, H3K18ub enhances SUV39H1/H2 methyltransferase activity and, in colon cancer cells, nucleates new H3K9me3 domains at CpG island promoters of DNA methylation-silenced tumor suppressor genes. Disrupting UHRF1 enzyme activity prevents H3K9me3 accumulation while promoting PRC2-dependent H3K27me3 as a tertiary layer of gene repression in these regions. In contrast, disrupting H3K18ub-dependent SUV39H1/H2 activity enhances the transcriptional activating and antiproliferative effects of DNMT1 inhibition. Collectively, these findings reveal roles for UHRF1 and H3K18ub in regulating a hierarchy of repressive histone methylation signaling and rationalize a combination strategy for epigenetic cancer therapy.

2024-12-03 | GSE282922 | GEO

Epigenetic reprogramming of the mesenchymal state by SUV39H1/H2 [ChIP-Seq]

Project description:Epigenetic reprogramming of the mesenchymal state by SUV39H1/H2 [ChIP-Seq]

| PRJNA851827 | ENA