Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA308368 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The generation of induced pluripotent stem cells (iPSCs) from differentiated cells following forced expression of Oct4, Klf4, Sox2 and c-Myc (OKSM) is slow and inefficient, suggesting that transcription factors have to overcome somatic barriers that resist cell fate change. Here, we performed an ubiased serial shRNA enrichment screen to identify novel repressors of somatic cell reprogramming into iPSCs. This effort uncovered the sumoylation effector protein Sumo2 as one of the strongest roadblocks to iPSC formation. Depletion of Sumo2 both enhances and accelerates reprogramming, yielding transgene-independent, chimera-competent iPSCs after as little as 36 hours of OKSM expression. We further show that the Sumo2 pathway acts independently of exogenous c-Myc expression and in parallel with small molecule enhancers of reprogramming. Critically, suppression of SUMO2 also promotes the generation of human iPSCs. Together, our results reveal sumoylation as a crucial post-transcriptional mechanism that resists the acquisition of pluripotency from fibroblasts using defined factors. Microarray analysis was performed during reprogramming or of iPSC lines derived upon Sumo2 knockdown Total RNA was isolated from day 6 reprogramming fibroblasts with or without Sumo2 knockdown; as well as stable iPSC clones derived from Sumo2 knockdown fibroblasts.
2016-03-03 | E-GEOD-76699 | biostudies-arrayexpress
Project description:The generation of induced pluripotent stem cells (iPSCs) from differentiated cells following forced expression of Oct4, Klf4, Sox2 and c-Myc (OKSM) is slow and inefficient, suggesting that transcription factors have to overcome somatic barriers that resist cell fate change. Here, we performed an ubiased serial shRNA enrichment screen to identify novel repressors of somatic cell reprogramming into iPSCs. This effort uncovered the sumoylation effector protein Sumo2 as one of the strongest roadblocks to iPSC formation. Depletion of Sumo2 both enhances and accelerates reprogramming, yielding transgene-independent, chimera-competent iPSCs after as little as 36 hours of OKSM expression. We further show that the Sumo2 pathway acts independently of exogenous c-Myc expression and in parallel with small molecule enhancers of reprogramming. Critically, suppression of SUMO2 also promotes the generation of human iPSCs. Together, our results reveal sumoylation as a crucial post-transcriptional mechanism that resists the acquisition of pluripotency from fibroblasts using defined factors. Microarray analysis was performed during reprogramming or of iPSC lines derived upon Sumo2 knockdown
2016-03-03 | GSE76699 | GEO
Project description:SUMOylation has emerged as a key regulator of chromatin and transcription, yet its contribution to lineage reprogramming remains unclear. To explore how chromatin SUMOylation influences cellular plasticity, we studied CEBPA-driven lineage reprogramming of human leukemic B-cells into macrophage-like cells. By integrating ChIP-seq, ATAC-seq, RNA-seq and chromatin-directed proteomics, we mapped the chromatin landscape and transcriptomic changes during early reprogramming. Lineage conversion triggered a dynamic rise in SUMO2/3 chromatin occupancy at CEBPA-bound sites, revealing a coordinated regulatory mechanism. Proteomic profiling of SUMO2/3- and CEBPA-associated chromatin uncovered extensive convergence and enrichment of differentiation-related transcription factors, chromatin remodelers and coregulators. Among these, NCOA3 displayed markedly increased SUMO2/3 association upon lineage conversion. NCOA3 co-occupied CEBPA- and SUMO2/3-bound chromatin regions, implying a SUMOylation-supported coregulatory role in lineage reprogramming. Pharmacological inhibition of SUMOylation using ML-792 (SUMOi) selectively enhanced CEBPA chromatin occupancy and chromatin accessibility, altered the CEBPA association of proteins, and modified NCOA3 binding dynamics. SUMOi also reshaped gene expression, promoting loss of B-cell identity and activation of macrophage-associated programs, including lipid metabolism. Collectively, our findings highlight chromatin SUMOylation as a dynamic and context-dependent modifier that fine-tunes lineage transitions, with implications for chromatin biology and therapeutic modulation of cell identity.
2026-05-27 | GSE311975 | GEO
Project description:SUMOylation has emerged as a key regulator of chromatin and transcription, yet its contribution to lineage reprogramming remains unclear. To explore how chromatin SUMOylation influences cellular plasticity, we studied CEBPA-driven lineage reprogramming of human leukemic B-cells into macrophage-like cells. By integrating ChIP-seq, ATAC-seq, RNA-seq and chromatin-directed proteomics, we mapped the chromatin landscape and transcriptomic changes during early reprogramming. Lineage conversion triggered a dynamic rise in SUMO2/3 chromatin occupancy at CEBPA-bound sites, revealing a coordinated regulatory mechanism. Proteomic profiling of SUMO2/3- and CEBPA-associated chromatin uncovered extensive convergence and enrichment of differentiation-related transcription factors, chromatin remodelers and coregulators. Among these, NCOA3 displayed markedly increased SUMO2/3 association upon lineage conversion. NCOA3 co-occupied CEBPA- and SUMO2/3-bound chromatin regions, implying a SUMOylation-supported coregulatory role in lineage reprogramming. Pharmacological inhibition of SUMOylation using ML-792 (SUMOi) selectively enhanced CEBPA chromatin occupancy and chromatin accessibility, altered the CEBPA association of proteins, and modified NCOA3 binding dynamics. SUMOi also reshaped gene expression, promoting loss of B-cell identity and activation of macrophage-associated programs, including lipid metabolism. Collectively, our findings highlight chromatin SUMOylation as a dynamic and context-dependent modifier that fine-tunes lineage transitions, with implications for chromatin biology and therapeutic modulation of cell identity.
2026-05-27 | GSE311971 | GEO
Project description:SUMOylation has emerged as a key regulator of chromatin and transcription, yet its contribution to lineage reprogramming remains unclear. To explore how chromatin SUMOylation influences cellular plasticity, we studied CEBPA-driven lineage reprogramming of human leukemic B-cells into macrophage-like cells. By integrating ChIP-seq, ATAC-seq, RNA-seq and chromatin-directed proteomics, we mapped the chromatin landscape and transcriptomic changes during early reprogramming. Lineage conversion triggered a dynamic rise in SUMO2/3 chromatin occupancy at CEBPA-bound sites, revealing a coordinated regulatory mechanism. Proteomic profiling of SUMO2/3- and CEBPA-associated chromatin uncovered extensive convergence and enrichment of differentiation-related transcription factors, chromatin remodelers and coregulators. Among these, NCOA3 displayed markedly increased SUMO2/3 association upon lineage conversion. NCOA3 co-occupied CEBPA- and SUMO2/3-bound chromatin regions, implying a SUMOylation-supported coregulatory role in lineage reprogramming. Pharmacological inhibition of SUMOylation using ML-792 (SUMOi) selectively enhanced CEBPA chromatin occupancy and chromatin accessibility, altered the CEBPA association of proteins, and modified NCOA3 binding dynamics. SUMOi also reshaped gene expression, promoting loss of B-cell identity and activation of macrophage-associated programs, including lipid metabolism. Collectively, our findings highlight chromatin SUMOylation as a dynamic and context-dependent modifier that fine-tunes lineage transitions, with implications for chromatin biology and therapeutic modulation of cell identity.
2026-05-27 | GSE311969 | GEO
Project description:Tumor suppressor p14ARF is a lysine-less protein that suppresses tumorigenesis through different mechanisms, including enhancing the SUMOylation of its interactors. Although p14ARF is known to interact with the SUMO conjugating enzyme UBC9, the link between ARF and SUMOylation is poorly understood and the potential impact of SUMOylation on p14ARF is unknown. Herein, we show that p14ARF is modified by SUMO2 in vitro, both in transfected cells and under endogenous conditions. SUMO conjugates to the N-terminal part of the tumor suppressor protein increasing its stability. Degradation of p14ARF protein is induced by UBC9 downmodulation or the inhibition of SUMOylation, and is rescued by the NEDDylation inhibitor MLN4924. Treatment with MLN4924 also promotes p14ARF SUMOylation and the transcriptional transactivation of the SUMOylation machinery components SUMO1, SUMO2 and UBC9. This causes a global increase in SUMOylation that contributesto the upregulation of p14ARF levels. Importantly, p14ARF is required for the global increase in SUMOylation induced by MLN4924, and it plays an important role in the cytotoxic effect of the NEDDylation inhibitor on prostate cancer cells. Our results provide evidence that lysine-independent SUMOylation of p14ARF is a new post-translational mechanism regulating p14ARF stability and establishes a new link between inhibition of NEDDylation and SUMOylation.
2025-07-30 | GSE278308 | GEO
Project description:Heat shock induces rapid modification of proteins with SUMO2/3. This study concentrated in charaterizing how these changes are reflected on SUMOylation of chromatin bound proteins, trancsription, and chromatin binding of SUMO ligase PIAS1. Comparison of chromatin SUMO2/3 modification pattern in non-stressed and heat shocked K562 and VCaP cells. All samples were done as biological replicates. In K562 cells, SUMO2/3 ChIP-seq was done in non-stressed (37C) and heat shocked (30min at 43C) cells. The effect of heat shock factor 1 (HSF1) to chromatin SUMOylation in HS was studied in HSF1 silenced (shHSF1) K562 cells (non-stressed vs. heat shocked) using scramble shRNA transfected cells as control (shSCR). SUMO2/3, SUMO ligase PIAS1,and RNA polymerase II binding in HS (30 min at 43C) and recovery from HS (1h at 37C after HS) was studied using ChIP-seq. Effect of PIAS1 for chromatin SUMOylation was studied in PIAS1 silenced (siRNA for PIAS1, siPIAS1) cells (non-stressed or heat shocked) using non-targeting siRNA transfected cells as a control (siNON). Effect of SUMOylation to chromatin binding of RNA polymerase II was studied in UBE2I silenced (siRNA for UBE2I) and control (non-targeting siRNA transfected, siNON) VCaP cells (non-stressed or heat shocked). Effect of transtription inhibition for chromatin SUMOylation was studied in TRP (triptolide; 1 micromolar, 3h) and DRB (5,6-Dichlorobenzimidazole 1-beta-D-ribofuranosidase; 100 micromolar, 3h) treated VCaP cells. GRO-seq was used to determine HS-induced changes in nascent transcription in K562 cells.
2015-07-02 | E-GEOD-66448 | biostudies-arrayexpress
Project description:Purpose: To determine SUMO1 and SUMO2 chromatin profile in a static and dynamic manner in BMDC before and after LPS stimulation, and to determine RNAPolII chromatin occupancy in sumoylation-deficient BMDC compared to wild-type cells. Methods: SUMO1, SUMO2 and RNAPolII chromatin profiles were determined by sequencing BMDC chromatin immunoprecipitated with antibodies specific for SUMO1, SUMO2 and RNAPolII before and after LPS stimulation. Results: We show dynamic occupancy of three distal sites upstream of Ifnb1 gene by SUMO1 and SUMO2, as well as increased RNAPolII recruitment on selected genes. Conclusions: SUMO acts as a regulator of inflammatory and anti-viral gene programs. A study of SUMO and RNAPolII chromatin profile in Bone Marrow derived Dendritic Cells.
2015-12-14 | E-GEOD-66315 | biostudies-arrayexpress
Project description:SUMOylation is a dynamic post-translational protein modification that primarily takes place in cell nuclei, where it plays a key role in multiple DNA-related processes. In brain cells, and particularly in neurons, mostly nuclear proteins are SUMOylated, and the SUMOylation-dependent control of a subset of neuronal transcription factors is known to regulate various aspects of nerve cell differentiation, development, and function. In an unbiased screen for endogenous SUMOylation targets in the developing mouse brain, we previously identified the transcription factor Zbtb20 as a new SUMO1 conjugate. We show here that the three key SUMO paralogues SUMO1, SUMO2, and SUMO3 can all be conjugated to Zbtb20 in vitro, and we confirm the SUMOylation of Zbtb20 in vivo. Using primary hippocampal neurons as a model system, we then demonstrate that the expression of Zbtb20 is required for proper nerve cell development and neurite growth and branching. Furthermore, we show that the SUMOylation of Zbtb20 is essential for Zbtb20 function in this context, and provide evidence indicating that SUMOylation affects the Zbtb20-dependent transcriptional profile of neurons. Taken together, our data highlight the role of SUMOylation in the regulation of neuronal transcription factors that determine nerve cell development. Specifically, our data demonstrate that key functions of the transcription factor Zbtb20 in neuronal development and neurite growth are under the obligatory control of SUMOylation.
2021-01-06 | GSE143926 | GEO