Accession | PRJCA001144 | ||||||||||||||||
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Title | Enhancer reprogramming promotes TGFβ-induced epithelial-to-mesenchymal transition and cancer metastasis | ||||||||||||||||
Relevance | Medical | ||||||||||||||||
Data types |
Epigenomics
Transcriptome or Gene expression Raw sequence reads |
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Organisms |
Mus musculus
Homo sapiens |
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Description | The epithelial-to-mesenchymal transition (EMT) is a cellular process associated with tumor stemness, metastasis, and chemotherapy resistance, and the TGFβ signaling is a key pathway triggering EMT. However, the TGFβ-induced epigenetic reprogramming during EMT remains largely unknown. Here we reveal that HDAC1-mediated global histone deacetylation and the gain of specific H3K27ac-marked enhancer are essential for TGFβ-induced EMT process. Gained enhancers-associated genes upon TGFβ treatment are linked to gene activation of EMT markers and cancer metastasis. Through motif enrichment analysis for loss or gained enhancers upon TGFβ stimulation, we identify FOXA2 as a key factor for maintaining the epithelial-specific enhancer activity and epithelial competence, and we also find that TEAD4 could form a complex with SMAD2 to mediate TGFβ signaling-triggered enhancer reprogramming, cell migration, and EMT. Finally, the dynamic loss or gain enhancers-linked three-dimensional (3D) genome architecture transition is profoundly related to EMT process. Together, our results implicate that key transcription factor-mediated enhancer reprogramming modulates a retrograde developmental transition in TGFβ signaling-triggered cancer metastasis. | ||||||||||||||||
Sample scope | Multiisolate | ||||||||||||||||
Release date | 2020-06-30 | ||||||||||||||||
Publication |
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Grants |
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Submitter | Liye Zhang (zhangly@shanghaitech.edu.cn) | ||||||||||||||||
Organization | ShanghaiTech University | ||||||||||||||||
Submission date | 2018-11-24 |