Similar Datasets
Project description:Somatic cells can be reprogrammed to pluripotent stem cells through the addition of just four transcription factors, OCT4, SOX2, KLF4 and c-MYC (OSKM). Although OSKM initiates reprogramming it is clear that extensive epigenetic remodeling is required to complete reprogramming. Critically, OSKM do not directly activate gene expression but instead recruit co-activators and co-repressors that remodel the local chromatin and in some way make the cells permissive for reprogramming. Consequently understanding how epigenetic co-repressors and co-activators are involved in reprogramming is a critical step in understanding the reprogramming process in detail. In this study we explored the role of the lysine-specific demethylase Kdm6b/Jmjd3 and its role in the reprogramming of somatic cells to pluripotent cells.
2020-07-22 | GSE149500 | GEO
Project description:Somatic cells can be reprogrammed to pluripotent stem cells through the addition of just four transcription factors, OCT4, SOX2, KLF4 and c-MYC (OSKM). Although OSKM initiates reprogramming it is clear that extensive epigenetic remodeling is required to complete reprogramming. Critically, OSKM do not directly activate gene expression but instead recruit co-activators and co-repressors that remodel the local chromatin and in some way make the cells permissive for reprogramming. Consequently understanding how epigenetic co-repressors and co-activators are involved in reprogramming is a critical step in understanding the reprogramming process in detail. In this study we explored the role of the lysine-specific demethylase Kdm6b/Jmjd3 and its role in the reprogramming of somatic cells to pluripotent cells.
2020-07-22 | GSE74998 | GEO
Project description:Somatic cells can be reprogrammed to pluripotent stem cells through the addition of just four transcription factors, OCT4, SOX2, KLF4 and c-MYC (OSKM). Although OSKM initiates reprogramming it is clear that extensive epigenetic remodeling is required to complete reprogramming. Critically, OSKM do not directly activate gene expression but instead recruit co-activators and co-repressors that remodel the local chromatin and in some way make the cells permissive for reprogramming. Consequently understanding how epigenetic co-repressors and co-activators are involved in reprogramming is a critical step in understanding the reprogramming process in detail. In this study we explored the role of the lysine-specific demethylase Kdm6b/Jmjd3 and its role in the reprogramming of somatic cells to pluripotent cells.
2020-07-22 | GSE74997 | GEO
Project description:Transforming growth factor-β (TGF-β) signaling pathways are well-recognized for their role in proliferation and epithelial-mesenchymal transition (EMT) of cancer cells, but much less is understood about their contribution to interactions with other signaling events. Recent studies have indicated that crosstalk between TGF-β and Ras signaling makes a contribution to TGF-β-mediated EMT. Here, we demonstrate that Jumonji domain containing-3 (JMJD3 also called KDM6B) promotes TGF-β-mediated Smad activation and EMT in Ras-activated lung cancer cells. JMJD3 in lung cancer patients was significantly increased and JMJD3 expression in lung tumor tissues was correlated with expression of K-Ras or H-Ras in particular, and its expression was regulated by Ras activity in lung cancer cells. JMJD3 promotes TGF-β-induced Smad activation and EMT in Ras-activated lung cancer cells through the induction of syntenin, a protein that regulates TGF-β receptor activation upon ligand binding. Tissue array and ChIP analysis revealed that JMJD3 epigenetically induces syntenin expression by directly regulating H3K27 methylation levels. Mechanical exploration identified a physical and functional association of JMJD3 with syntenin presiding over the TGF-β in Ras-activated lung cancer cells. Taken together, these findings provide new insight into the mechanisms by which JMJD3 promotes syntenin expression resulting in oncogenic Ras cooperation with TGF-β to promote EMT.
| S-EPMC7910473 | biostudies-literature
Project description:The growth factor and cytokine regulated transcription factor STAT3 is required for the self-renewal of several stem cell types including tumor stem cells from glioblastoma. Here we show that STAT3 inhibition leads to the upregulation of the histone H3K27me2/3 demethylase Jmjd3 (KDM6B), which can reverse polycomb complex-mediated repression of tissue specific genes. STAT3 binds to the Jmjd3 promoter, suggesting that Jmjd3 is a direct target of STAT3. Overexpression of Jmjd3 slows glioblastoma stem cell growth and neurosphere formation, whereas knockdown of Jmjd3 rescues the STAT3 inhibitor-induced neurosphere formation defect. Consistent with this observation, STAT3 inhibition leads to histone H3K27 demethylation of neural differentiation genes, such as Myt1, FGF21, and GDF15. These results demonstrate that the regulation of Jmjd3 by STAT3 maintains repression of differentiation specific genes and is therefore important for the maintenance of self-renewal of normal neural and glioblastoma stem cells.
| S-EPMC5383422 | biostudies-literature
Project description:Role of the histone demethylase Kdm6b/Jmjd3 in somatic cell reprogramming
| PRJNA302168 | ENA
Project description:Acute myeloid leukemia (AML) is a heterogeneous disease with poor outcomes. Despite increased evidence shows that dysregulation of histone modification contributes to AML, specific drugs targeting key histone modulators are not applied in the clinical treatment of AML. Here, we investigated whether targeting KDM6B, the demethylase of tri-methylated histone H3 lysine 27 (H3K27me3), has a therapeutic potential for AML.A KDM6B-specific inhibitor, GSK-J4, was applied to treat the primary cells from AML patients and AML cell lines in vitro and in vivo. RNA-sequencing was performed to reveal the underlying mechanisms of inhibiting KDM6B for the treatment of AML.Here we observed that the mRNA expression of KDM6B was up-regulated in AML and positively correlated with poor survival. Treatment with GSK-J4 increased the global level of H3K27me3 and reduced the proliferation and colony-forming ability of primary AML cells and AML cell lines. GSK-J4 treatment significantly induced cell apoptosis and cell-cycle arrest in Kasumi-1 cells, and displayed a synergistic effect with cytosine arabinoside. Notably, injection of GSK-J4 attenuated the disease progression in a human AML xenograft mouse model in vivo. Treatment with GSK-J4 predominantly resulted in down-regulation of DNA replication and cell-cycle-related pathways, as well as abrogated the expression of critical cancer-promoting HOX genes. ChIP-qPCR validated an increased enrichment of H3K27me3 in the transcription start sites of these HOX genes.In summary, our findings suggest that targeting KDM6B with GSK-J4 has a therapeutic potential for the treatment of AML.
| S-EPMC5948279 | biostudies-literature
Project description:Role of the histone demethylase Kdm6b/Jmjd3 in somatic cell reprogramming [ATAC-Seq]
| PRJNA628934 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-01-31 | E-GEOD-59695 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-02-22 | E-GEOD-70729 | biostudies-arrayexpress