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JUNB O-GlcNAcylation-mediated Promoter Accessibility of Metabolic Genes Modulates Distinct Epithelial Lineage in Pulmonary Fibrosis

GSE281994 Homo sapiens Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2024/12/17 Platform GPL24676
Summary
Harnessing a 3D patient derived organoid model and multi-omics approach, we provide the first inventory of the connection between metabolic alteration, chromatin accessibility, and transcriptional regulation in IPF aberrant epithelial remodeling. This remodeling is characterized by an increase in chromatin accessibility, particularly at JUNB motif-enriched promoter regions proximal to transcription start sites of metabolic and pro-fibrotic genes. Mechanistically, JUNB undergoes O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), a critical step in modulating pro-fibrotic responses to chronic injury. This modification is pivotal in fostering the emergence of aberrant epithelial basal cells in the alveolar niche, a proposed driver of IPF pathology. Our findings reveal a novel link between metabolic dysregulation and cell fate regulation at the chromatin level in fibrosis, mediated by the O-GlcNAc-JUNB axis.
Published in
JUNB O-GlcNAcylation-Mediated Promoter Accessibility of Metabolic Genes Modulates Distinct Epithelial Lineage in Pulmonary Fibrosis
Bammert MT, Ansari M, Haag L et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2025 · PMID 39676507 · doi:10.1002/advs.202406751
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Also filed as BioProject PRJNA1186577 and SRA study SRP545447. Searching any of these in the dataset finder brings you back here.

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