Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA317447 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The histone demethylase KDM6A controls the mammary luminal lineage through enzyme-independent mechanisms
| PRJNA310874 | ENA
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:KDM6A (UTX) controls the balance of basal and luminal mammary epithelium through regulating lineage-specific genes independent of its demethylase activity
| PRJNA306480 | ENA
Project description:We demonstrate that the histone demethylase KDM6A promotes infection of diverse coronaviruses, including SARS-CoV-1, SARS-CoV-2, MERS-CoV and mouse hepatitis virus (MHV) in a demethylase activity-independent manner
2023-04-10 | GSE228268 | 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:Mutations in genes encoding critical epigenetic regulators are frequently noted in bladder cancer, however, the mechanisms by which these alterations impact the therapeutic response remain incompletely understood. Through retrospective analyses of multiple bladder cancer patient cohorts, we identified that loss-of-function mutations in KDM6A, a histone demethylase altered in approximately 26% of advanced bladder cancers, are associated with reduced overall survival following cisplatin-based chemotherapy whereas they correlate with improved outcomes with anti–PD-1/anti–PD-L1 therapy. To elucidate the biological underpinnings of this divergent clinical response, we conducted reverse translational mechanistic studies using human bladder cancer cell lines harboring mutations in KDM6A gene and CRISPR-Cas9–mediated deletion of Kdm6a in murine bladder cancer models. We found that KDM6A deficiency drives cisplatin resistance via increased generation of extrachromosomal circular DNA (eccDNA) carrying oncogenes linked to drug resistance. Additionally, KDM6A directly regulates DNA mismatch and double-strand break repair genes, and its loss impairs these pathways in both human and murine bladder cancer cells. Concurrently, KDM6A loss alters tumor metabolism, suppressing glycolysis and lactate production, which in turn diminishes histone lactylation (H3K9la, H3K18la) in regulatory T cells (Tregs). This leads to decreased expression of key immune-suppressive genes, including Foxp3, Tgfb, and Pdcd1. Consequently, reduced expansion of PD-1hi Tregs enhances the cytotoxic T cell-to-Treg ratio, improving the response to anti-PD-1 therapy in Kdm6a-deficient tumor-bearing mice. Collectively, these findings establish KDM6A as a key epigenetic regulator of genomic integrity and the immunosuppressive tumor microenvironment and provide a mechanistic rationale for utilizing KDM6A mutation status as a predictive biomarker to guide personalized treatment strategies in advanced bladder cancer.
2025-12-04 | PXD065234 | Pride
Project description:Here we describe the application of high-throughput sequencing technology for profiling histone and DNA methylation, and gene expression patterns of normal human mammary progenitor-enriched and luminal lineage-committed cells. We observed significant differences in histone H3 lysine 27 tri-methylation (H3K27me3) enrichment and DNA methylation of genes expressed in a cell type-specific manner, suggesting their regulation by epigenetic mechanisms and a dynamic interplay between the two processes that together define developmental potential. The technologies we developed and the epigenetically regulated genes we identified will accelerate the characterization of primary cell epigenomes and the dissection of human mammary epithelial lineage-commitment and luminal differentiation. Global profiling of differentially methylated regions in 2 cell types from 6 individuals.
2011-03-01 | E-GEOD-26139 | biostudies-arrayexpress
Project description:Here we describe the application of high-throughput sequencing technology for profiling histone and DNA methylation, and gene expression patterns of normal human mammary progenitor-enriched and luminal lineage-committed cells. We observed significant differences in histone H3 lysine 27 tri-methylation (H3K27me3) enrichment and DNA methylation of genes expressed in a cell type-specific manner, suggesting their regulation by epigenetic mechanisms and a dynamic interplay between the two processes that together define developmental potential. The technologies we developed and the epigenetically regulated genes we identified will accelerate the characterization of primary cell epigenomes and the dissection of human mammary epithelial lineage-commitment and luminal differentiation. Global transcriptome profilings of 15 samples in normal breast tissue using Sage-Seq.
2011-03-01 | E-GEOD-26140 | biostudies-arrayexpress
Project description:Here we describe the application of high-throughput sequencing technology for profiling histone and DNA methylation, and gene expression patterns of normal human mammary progenitor-enriched and luminal lineage-committed cells. We observed significant differences in histone H3 lysine 27 tri-methylation (H3K27me3) enrichment and DNA methylation of genes expressed in a cell type-specific manner, suggesting their regulation by epigenetic mechanisms and a dynamic interplay between the two processes that together define developmental potential. The technologies we developed and the epigenetically regulated genes we identified will accelerate the characterization of primary cell epigenomes and the dissection of human mammary epithelial lineage-commitment and luminal differentiation. Examination of histone H3K27me3 modifications in 2 cell types from 3 individuals and H3K4me3 modifications in 2 cell types from one individual sample.
2011-03-01 | E-GEOD-26137 | biostudies-arrayexpress
Project description:KDM6A is a histone demethylase that remove H3K27me3 lysine. This study compares the histone modification pattern between WT and KDM6A KO cells.
2022-03-03 | GSE168249 | GEO