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

Publication

PubMed ID	Article title	Journal name	DOI	Year
32526202	Enhancer Reprogramming within Pre-existing Topologically Associated Domains Promotes TGF-Î²-Induced EMT and Cancer Metastasis	Molecular Therapy	10.1016/j.ymthe.2020.05.026	2020

Grants

Agency	program	Grant ID
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	-
SAMC053334	A549_TEAD4 shRNA_TGFb_H3K27ac ChIP-seq
SAMC053333	A549_TEAD2 shRNA_TGFb_H3K27ac ChIP-seq
SAMC053332	A549_shRNA control replicate 2_TGFb_H3K27ac ChIP-seq
SAMC053331	A549_TEAD4 shRNA_H3K27ac ChIP-seq
SAMC053330	A549_TEAD2 shRNA_H3K27ac ChIP-seq
SAMC053329	A549_GFP control_H3K27ac ChIP-seq
SAMC053328	A549_FOXA2 shRNA2_H3K27ac ChIP-seq
SAMC053327	A549_shRNA control replicate 1_H3K27ac ChIP-seq
SAMC053326	A549_TEAD4 shRNA_input
SAMC053325	A549_TEAD2 shRNA_input
SAMC053324	A549_shRNA control replicate 2_input
SAMC053323	A549_FOXA2 OE_input
SAMC053322	A549_GFP control_input
SAMC053321	A549_shRNA control replicate 2_H3K27ac ChIP-seq
SAMC053320	A549_FOXA2 OE_H3K27ac ChIP-seq
SAMC053319	A549_FOXA2 shRNA2_input
SAMC053318	A549_shRNA control replicate 1_input
SAMC053317	A549_control_Input
SAMC053316	A549_TGFb_Input
SAMC053315	A549_H3K4me3 ChIP-seq
SAMC053314	A549_TGFb_H3K4me3 ChIP-seq
SAMC053313	A549_H3K27ac ChIP-seq
SAMC053312	A549_H3K4me1 ChIP-seq
SAMC053311	A549_TGFb_H3K27ac ChIP-seq
SAMC053310	A549_TGFb_H3K4me1 ChIP-seq
SAMC053309	A549_TGFb
SAMC053308	A549
SAMC053307	A549_shRNA control_TGFb
SAMC053306	A549_shRNA control_rep2
SAMC053305	A549_TEAD4 shRNA
SAMC053304	A549_TEAD4 shRNA_TGFb
SAMC053303	A549_TEAD2 shRNA
SAMC053302	A549_TEAD2 shRNA_TGFb
SAMC053301	A549_shRNA control_rep1
SAMC053300	A549_FOXA2 shRNA2
SAMC053299	A549_FOXA2 shRNA1
SAMC053298	A549_GFP
SAMC053297	A549_GFP_TGFb
SAMC053296	A549_FOXA2 OE
SAMC053295	A549_FOXA2 OE_TGFb
SAMC053294	HiC-TGFb rep2
SAMC053293	HiC-TGFb rep1
SAMC053292	HiC-control rep2
SAMC053291	HiC-control rep1
SAMC053290	AML12 _TGFb_ MS275
SAMC053289	AML12_MS275
SAMC053288	AML12_TGFb
SAMC053287	AML12_DMSO
GSA (1)	-
CRA001325	Enhancer reprogramming promotes TGFβ-induced epithelial-to-mesenchymal transition and cancer metastasis