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Role of histone demethylase Kdm6a in pancreatic cancer (ChIP-Seq)

GSE98568 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 9 samples Submitted 2018/04/01 Platform GPL17021
Summary
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.
Published in
Loss of KDM6A Activates Super-Enhancers to Induce Gender-Specific Squamous-like Pancreatic Cancer and Confers Sensitivity to BET Inhibitors
Andricovich J, Perkail S, Kai Y et al. · Cancer cell 2018 · PMID 29533787 · doi:10.1016/j.ccell.2018.02.003
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Also filed as BioProject PRJNA385528 and SRA study SRP106494. Searching any of these in the dataset finder brings you back here.

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