Accession PRJCA001144
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
Organisms Mus musculus
Homo sapiens
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
Grants
Agency program Grant ID Grant title
Ministry of Science and Technology of the People's Republic of China (MOST) National Key Technologies R&D Program 2016YFC0905900
Ministry of Science and Technology of the People's Republic of China (MOST) National Key Technologies R&D Program 2017YFC1001300
National Natural Science Foundation of China (NSFC) 31771130
Submitter Liye    Zhang  (zhangly@shanghaitech.edu.cn)
Organization ShanghaiTech University
Submission date 2018-11-24

Project Data

Resource name Description
BioSample (48)  show -
GSA (1) -
CRA001325 Enhancer reprogramming promotes TGFβ-induced epithelial-to-mesenchymal transition and cancer metastasis