SUV39H1 regulates KLF4 and chromatin remodeling in smooth muscle cell phenotypic plasticity [ATAC-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE298511 | GEO | 2026/05/01
REPOSITORIES: GEO
Similar Datasets
Project description:We investigated the role of SUV39H1, KDM4A, and TET2 in vascular smooth muscle cell (VSMC) plasticity.
2026-05-01 | GSE298510 | GEO
Project description:SUV39H1 regulates KLF4 and chromatin remodeling in smooth muscle cell phenotypic plasticity [ATAC-Seq]
| PRJNA1269583 | ENA
Project description:SUV39H1 regulates KLF4 and chromatin remodeling in smooth muscle cell phenotypic plasticity [RNA-Seq]
| PRJNA1269584 | ENA
Project description:Histone H3 mono-ubiquitination, catalyzed by the RING E3 ubiquitin ligase UHRF1, is appreciated as a docking site for DNMT1 during DNA replication to facilitate DNA methylation maintenance. Its functions beyond this are unknown. Here, we identify simultaneous increases in UHRF1-dependent H3K18ub and SUV39H1/2-dependent H3K9me3 as prominent epigenetic alterations accompanying DNA hypomethylation induced by DNMT1 inhibition. Integrative epigenomics analyses reveal that transient accumulation of hemi-methylated DNA, resulting from incomplete DNA methylation maintenance, stimulates UHRF1-dependent H3K18ub at CpG islands that nucleates new domains of H3K9me3 and impedes PRC2 activity in these genomic regions. Notably, H3K18ub enhances the methyltransferase activity of SUV39H1/2, leading to increased H3K9me3 at these CpG island promoters. Blocking H3K18ub-dependent SUV39H1/2 activity enhances the efficacy of DNMT1 inhibitors. Collectively, these findings reveal a novel histone ubiquitination-methylation crosstalk mechanism that reinforces heterochromatin states in the absence of DNA methylation and proposes new strategies for improving cancer epigenetic therapy.
2024-12-02 | PXD049993 | Pride
Project description:Histone 3 Lysine 9 tri-methylation (H3K9me3) is a heterochromatin-associated histone mark deposited broadly across the genome and its regulation is required in normal hematopoiesis. Furthermore, H3K9me3 has been linked with 3D genome organization. However, in the context of acute myeloid leukemia (AML), the regulation of H3K9me3 and its function in 3D genome architecture remained understudied. In this study, through systematic Knockdowns and Knockouts, we identified SUV39H1 and by part its paralogue SUV39H2 as the major H3K9me3 depositors in AML. We demonstrated the role of SUV39H1/2 in establishing global H3K9me3 levels in AML cells and showed H3K9me3 depletion upon SUV39H1/2 Knockout preferentially occurred at sub-megabase level broad peaks and in GC poor regions. Loss of SUV39H1/2-mediated H3K9me3 poised AML cells towards monocyte/macrophage differentiation, induced TE re-activation and interferon response activation, and reduced AML cell growth and clonogenicity in vitro. Analysis of higher-order chromatin architecture reveals that while SUV39H1/2-mediated H3K9me3 is associated with a small fraction of larger chromatin structures, loss of SUV39H1/2 drives concomitant increase of H3K27me3 at B compartments. Taken together, our findings characterize the regulation of SUV39H1/2-mediated H3K9me3 and reveal its role in leukemogenesis and higher-order chromatin structure.
2026-06-17 | GSE285123 | GEO
Project description:Histone 3 Lysine 9 tri-methylation (H3K9me3) is a heterochromatin-associated histone mark deposited broadly across the genome and its regulation is required in normal hematopoiesis. Furthermore, H3K9me3 has been linked with 3D genome organization. However, in the context of acute myeloid leukemia (AML), the regulation of H3K9me3 and its function in 3D genome architecture remained understudied. In this study, through systematic Knockdowns and Knockouts, we identified SUV39H1 and by part its paralogue SUV39H2 as the major H3K9me3 depositors in AML. We demonstrated the role of SUV39H1/2 in establishing global H3K9me3 levels in AML cells and showed H3K9me3 depletion upon SUV39H1/2 Knockout preferentially occurred at sub-megabase level broad peaks and in GC poor regions. Loss of SUV39H1/2-mediated H3K9me3 poised AML cells towards monocyte/macrophage differentiation, induced TE re-activation and interferon response activation, and reduced AML cell growth and clonogenicity in vitro. Analysis of higher-order chromatin architecture reveals that while SUV39H1/2-mediated H3K9me3 is associated with a small fraction of larger chromatin structures, loss of SUV39H1/2 drives concomitant increase of H3K27me3 at B compartments. Taken together, our findings characterize the regulation of SUV39H1/2-mediated H3K9me3 and reveal its role in leukemogenesis and higher-order chromatin structure.
2026-06-17 | GSE291238 | GEO
Project description:Histone 3 Lysine 9 tri-methylation (H3K9me3) is a heterochromatin-associated histone mark deposited broadly across the genome and its regulation is required in normal hematopoiesis. Furthermore, H3K9me3 has been linked with 3D genome organization. However, in the context of acute myeloid leukemia (AML), the regulation of H3K9me3 and its function in 3D genome architecture remained understudied. In this study, through systematic Knockdowns and Knockouts, we identified SUV39H1 and by part its paralogue SUV39H2 as the major H3K9me3 depositors in AML. We demonstrated the role of SUV39H1/2 in establishing global H3K9me3 levels in AML cells and showed H3K9me3 depletion upon SUV39H1/2 Knockout preferentially occurred at sub-megabase level broad peaks and in GC poor regions. Loss of SUV39H1/2-mediated H3K9me3 poised AML cells towards monocyte/macrophage differentiation, induced TE re-activation and interferon response activation, and reduced AML cell growth and clonogenicity in vitro. Analysis of higher-order chromatin architecture reveals that while SUV39H1/2-mediated H3K9me3 is associated with a small fraction of larger chromatin structures, loss of SUV39H1/2 drives concomitant increase of H3K27me3 at B compartments. Taken together, our findings characterize the regulation of SUV39H1/2-mediated H3K9me3 and reveal its role in leukemogenesis and higher-order chromatin structure.
2026-06-17 | GSE285125 | GEO
Project description:Histone 3 Lysine 9 tri-methylation (H3K9me3) is a heterochromatin-associated histone mark deposited broadly across the genome and its regulation is required in normal hematopoiesis. Furthermore, H3K9me3 has been linked with 3D genome organization. However, in the context of acute myeloid leukemia (AML), the regulation of H3K9me3 and its function in 3D genome architecture remained understudied. In this study, through systematic Knockdowns and Knockouts, we identified SUV39H1 and by part its paralogue SUV39H2 as the major H3K9me3 depositors in AML. We demonstrated the role of SUV39H1/2 in establishing global H3K9me3 levels in AML cells and showed H3K9me3 depletion upon SUV39H1/2 Knockout preferentially occurred at sub-megabase level broad peaks and in GC poor regions. Loss of SUV39H1/2-mediated H3K9me3 poised AML cells towards monocyte/macrophage differentiation, induced TE re-activation and interferon response activation, and reduced AML cell growth and clonogenicity in vitro. Analysis of higher-order chromatin architecture reveals that while SUV39H1/2-mediated H3K9me3 is associated with a small fraction of larger chromatin structures, loss of SUV39H1/2 drives concomitant increase of H3K27me3 at B compartments. Taken together, our findings characterize the regulation of SUV39H1/2-mediated H3K9me3 and reveal its role in leukemogenesis and higher-order chromatin structure.
2026-06-17 | GSE285122 | GEO
Project description:Oncogene-induced senescence (OIS), a terminal cell cycle block countering (pre)neoplastic lesions, is characterised on the molecular level by trimethylated histone H3 lysine 9 (h3K9me3), a transcriptionally repressive chromatin mark linked to silencing of S-phase-promoting genes. Whether H3K9-governed chromatin remodelling influences anticancer treatment-induced senescence (TIS) and whether functional control of this mark impacts on treatment outcome is not known. We used global gene expression profiling by microarrays to gain insight into the molecular responses of Emu-myc; Suv39h1-/- B-cell lymphoma cells to senescence-inducing anticancer agent Adriamycin (ADR). Primary lymphoma cells isolated from lymph nodes of Emu-Myc; Suv39h1-/- mice were used. In this model, the c-Myc oncogene is constitutively expressed in the cells of the B-cell lineage, leading to spontaneous development of aggressive B-cell lymphomas. Adriamycin (ADR), a cytostatic drug used as a standard part of several lymphoma treatment regimens, is known to massively induce TIS in Suv39h1-proficient lymphomas, protected from apoptosis by Bcl-2 over expression (Myc;Bcl2). In order to discern the impact of Suv39h1 to TIS induction under these conditions, we analysed here transcriptional profiles of matched pairs of Emu-myc;Suv39h1-/-;Bcl2 lymphomas, untreated or treated for 5 days with ADR.
2013-07-04 | E-GEOD-44355 | biostudies-arrayexpress
Project description:Vascular smooth muscle cell (VSMC) differentiation reprogramming plays an essential role in abdominal aortic aneurysm (AAA). However, the underlying mechanisms are still indistinct. FAM3A (family with sequence similarity 3, member A) is a newly identified metabolism regulator. We examined FAM3A expression and the downstream pathways affected by FAM3A in AAA, and how FAM3A regulated VSMC differentiation. We found that overexpression or supplement of FAM3A significantly attenuated the progression of AAA, manifested by maintenance of VSMC well-differentiation state and inhibition of VSMC transformation towards macrophage-, chondrocyte-, osteogenic-, mesenchymal-, and fibroblast-like cell subpopulations. Importantly, FAM3A induced a decrease in Krüppel-like factor 4 (KLF4) phosphorylation (Ser254) level, leading to its ubiquitination and a weakened nuclear localization. Our findings identify FAM3A as a novel VSMC fate-shaping regulator in AAA and unveil the underpinning mechanism associated with KLF4 ubiquitination and stability, which could develop new strategies based on FAM3A to restore VSMC homeostasis in AAA.
2023-04-23 | GSE230163 | GEO