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- Title
PHF13 epigenetically activates TGFβ driven epithelial to mesenchymal transition.
- Authors
Sun, Yating; Li, Dan; Liu, Hongmei; Huang, Yongye; Meng, Fanyu; Tang, Jiahao; Li, Zhanjun; Xie, Wanhua
- Abstract
Epigenetic alteration is a pivotal factor in tumor metastasis. PHD finger protein 13 (PHF13) is a recently identified epigenetic reader of H3K4me2/3 that functions as a transcriptional co-regulator. In this study, we demonstrate that PHF13 is required for pancreatic-cancer-cell growth and metastasis. Integrative analysis of transcriptome and epigenetic profiles provide further mechanistic insights into the epigenetic regulation of genes associated with cell metastasis during the epithelial-to-mesenchymal transition (EMT) induced by transforming growth factor β (TGFβ). Our data suggest PHF13 depletion impairs activation of TGFβ stimulated genes and correlates with a loss of active epigenetic marks (H3K4me3 and H3K27ac) at these genomic regions. These observations argue for a dependency of TGFβ target activation on PHF13. Furthermore, PHF13-dependent chromatin regions are enriched in broad H3K4me3 domains and super-enhancers, which control genes critical to cancer-cell migration and invasion, such as SNAI1 and SOX9. Overall, our data indicate a functional and mechanistic correlation between PHF13 and EMT.
- Publication
Cell Death & Disease, 2022, Vol 13, Issue 5, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-022-04940-4