Role of histone demethylase Kdm6a in pancreatic cancer
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PROVIDER: PRJNA383850 | ENA |
REPOSITORIES: ENA
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Project description:Role of histone demethylase Kdm6a in pancreatic cancer - ChIP-Seq
| PRJNA413702 | ENA
Project description:Transcriptional profile of murine Kdm6a null pancreatic cancer cell lines Loss-of-function mutations of KDM6A, an X chromosome encoded histone H3K27 demethylase, are frequent in a broad spectrum of epithelial and hematopoietic malignancies and contribute to oncogenesis with so far poorly characterized mechanisms. Pancreas specific ablation of Kdm6a in mice accelerated Kras-driven cell transformation and compromised survival in a gender specific manner. Female knockout animals were particularly vulnerable and developed aggressive squamous and quasi-mesenchymal tumors with metastatic potential, as opposed to males which developed adenocarcinomas and exhibited a better prognosis. Integration of gene expression studies coupled to ChIP-seq profiling of chromatin modifications demonstrated that loss of Kdm6a caused genome-wide remodeling of bivalent promoters and rewiring of enhancer chromatin to repress endodermal fate by activating c-MYC and TP63 dependent transcriptional programs favoring squamous and quasi-mesenchymal differentiation.
2018-04-01 | GSE98066 | GEO
Project description:Transcriptional profile of human pancreatic cancer cell lines trerated with JQ1 inhibitor. Loss-of-function mutations of KDM6A, an X chromosome encoded histone H3K27 demethylase, are frequent in a broad spectrum of epithelial and hematopoietic malignancies and contribute to oncogenesis with so far poorly characterized mechanisms. Pancreas specific ablation of Kdm6a in mice accelerated Kras-driven cell transformation and compromised survival in a gender specific manner. Female knockout animals were particularly vulnerable and developed aggressive squamous and quasi-mesenchymal tumors with metastatic potential, as opposed to males which developed adenocarcinomas and exhibited a better prognosis. Integration of gene expression studies coupled to ChIP-seq profiling of chromatin modifications demonstrated that loss of Kdm6a caused genome-wide remodeling of bivalent promoters and rewiring of enhancer chromatin to repress endodermal fate by activating c-MYC and TP63 dependent transcriptional programs favoring squamous and quasi-mesenchymal differentiation.
2018-04-01 | GSE98065 | GEO
Project description:Loss-of-function mutations of KDM6A, an X chromosome encoded histone H3K27 demethylase, are frequent in a broad spectrum of epithelial and hematopoietic malignancies and contribute to oncogenesis with so far poorly characterized mechanisms. Pancreas specific ablation of Kdm6a in mice accelerated Kras-driven cell transformation and compromised survival in a gender specific manner. Female knockout animals were particularly vulnerable and developed aggressive squamous and quasi-mesenchymal tumors with metastatic potential, as opposed to the males which developed adenocarcinomas and exhibited a better prognosis. Integration of gene expression studies coupled to ChIP-seq profiling of chromatin modifications demonstrated that loss of Kdm6a caused genome-wide remodeling of bivalent promoters and rewiring of enhancer chromatin to repress endodermal fate by activating c-MYC and TP63 dependent transcriptional programs favoring squamous and quasi-mesenchymal differentiation.
2018-04-01 | GSE104739 | GEO
Project description:Loss-of-function mutations of KDM6A, an X chromosome encoded histone H3K27 demethylase, are frequent in a broad spectrum of epithelial and hematopoietic malignancies and contribute to oncogenesis with so far poorly characterized mechanisms. Pancreas specific ablation of Kdm6a in mice accelerated Kras-driven cell transformation and compromised survival in a gender specific manner. Female knockout animals were particularly vulnerable and developed aggressive squamous and quasi-mesenchymal tumors with metastatic potential, as opposed to the males which developed adenocarcinomas and exhibited a better prognosis. Integration of gene expression studies coupled to ChIP-seq profiling of chromatin modifications demonstrated that loss of Kdm6a caused genome-wide remodeling of bivalent promoters and rewiring of enhancer chromatin to repress endodermal fate by activating c-MYC and TP63 dependent transcriptional programs favoring squamous and quasi-mesenchymal differentiation.
2018-04-01 | GSE98568 | GEO
Project description:The UTX/KDM6A gene encodes the UTX histone H3K27 demethylase, which plays an important role in mammalian development and is frequently mutated in cancers and particularly, in urothelial cancers. Using BioID technique, we explored the interactome of different UTX isoforms.
2024-01-28 | PXD041254 | Pride
Project description:Mammary ducts and alveoli are composed of basal and luminal cells, with the fate and differentiation of secreting cells being controlled by hormones through specific transcription factors. This study establishes the essential role of the histone H3 lysine 27 trimethylation (H3K27me3) demethylase KDM6A (UTX) in a balanced basal and luminal cell compartment. Disproportionate formation of basal cells in the absence of KDM6A resulted in disorganized mammary ducts and alveoli and lactation failure. Mutant luminal progenitors lost their distinctive transcription factor expression pattern and acquired basal characteristics leading to a preferential expansion of this lineage. The structure of mammospheres obtained from mutant progenitors suggested they were derived from basal progenitors. The genomic H3K27me3 landscape was unaltered in the absence of KDM6A suggesting demethylase-independent mechanisms. In support of this, mammary tissue developed normally in mice expressing a catalytically inactive KDM6A. This study demonstrated that mammary luminal progenitor cells rely on UTX to stably maintain their identity and thereby establish a balance of basal and luminal cells required for a functional mammary gland.
2016-06-06 | GSE77586 | GEO
Project description:Here we show binding and occupancy profiles for KDM6A, H3K27me3 and H3K4me3 to address the epigenetic regulation of a subset of Rhox genes, Rhox6 and 9, in female and male ES cells during differentiation. To further address a functional role for KDM6A in the epigenetic regulation of Rhox6 and 9, binding profiles for female ES cells treated with a control siRNA and siRNA specific for Kdm6a are shown. We report that two members of the Rhox cluster, Rhox6 and 9, are regulated by de-methylation of histone H3 at lysine 27 by KDM6A, a histone demethylase with female-biased expression. Our results are consistent with other homeobox genes in that Rhox6 and 9 are in bivalent domains prior to embryonic stem cell differentiation and thus poised for activation. In female mouse ES cells KDM6A is specifically recruited to Rhox6 and 9 for gene activation, a process inhibited by Kdm6a knockdown. In contrast, KDM6A occupancy at Rhox6 and 9 is low in male ES cells and knockdown has no effect on expression. Our study implicates Kdm6a, a gene that escapes X inactivation, in the regulation of genes important in reproduction, suggesting that KDM6A may play a role in the etiology of developmental and reproduction-related effects of X chromosome anomalies. ChIP-chip was used to analyze the binding profiles of KDM6A, H3K27me3, and H3K4me3 during differentiation in female and male ES cells. Additionally, ChiP-chip of KDM6A binding in control treated and siRNA treated ES cells is presented.
2013-03-22 | E-GEOD-45390 | biostudies-arrayexpress
Project description:Aberrant epigenetic reprogramming is one of the major barriers for somatic cell reprogramming. Although our previous study has demonstrated that KDM6A, a H3K27me3 demethylase, could improve nuclear reprogramming efficiency, but its role in somatic cell reprogramming and the mechanism remain unclear. In this study, we demonstrated that overexpression of Kdm6a could improve iPSC reprogramming efficiency in a demethylase enzymatic activity-dependent manner. And Kdm6a overexpression changed the gene expression profile and metabolic pattern through erasing the repressive H3K27me3 in fibroblast. Besides, we proved that KDM6A could promote IL-6 expression in MEF cells and the secreted IL-6 also could improve iPSC reprogramming efficiency. Furthermore, we found that KDM6A could promote PTEN expression, further regulate p-AKT and p-mTOR levels, which favor the reprogramming, and interference of PTEN could counteracted the promotion effect of KDM6A. Taken together, our data revealed that KDM6A could promote iPSC reprogramming efficiency by accelerate the change of gene expression profile and metabolic pattern in a demethylation-activity-dependent manner, which may give insight to the relationship between epigenetic modification and somatic cell reprogramming.
2021-10-20 | GSE138816 | GEO
Project description:Aberrant epigenetic reprogramming is one of the major barriers for somatic cell reprogramming. Although our previous study has demonstrated that KDM6A, a H3K27me3 demethylase, could improve nuclear reprogramming efficiency, but its role in somatic cell reprogramming and the mechanism remain unclear. In this study, we demonstrated that overexpression of Kdm6a could improve iPSC reprogramming efficiency in a demethylase enzymatic activity-dependent manner. And Kdm6a overexpression changed the gene expression profile and metabolic pattern through erasing the repressive H3K27me3 in fibroblast. Besides, we proved that KDM6A could promote IL-6 expression in MEF cells and the secreted IL-6 also could improve iPSC reprogramming efficiency. Furthermore, we found that KDM6A could promote PTEN expression, further regulate p-AKT and p-mTOR levels, which favor the reprogramming, and interference of PTEN could counteracted the promotion effect of KDM6A. Taken together, our data revealed that KDM6A could promote iPSC reprogramming efficiency by accelerate the change of gene expression profile and metabolic pattern in a demethylation-activity-dependent manner, which may give insight to the relationship between epigenetic modification and somatic cell reprogramming.
2021-10-20 | GSE138815 | GEO