Enhancer Reprogramming within Pre-existing Topologically Associated Domains Promotes TGF-beta-Induced EMT and Cancer Metastasis

doi:10.1016/j.ymthe.2020.05.026

	Enhancer Reprogramming within Pre-existing Topologically Associated Domains Promotes TGF-beta-Induced EMT and Cancer Metastasis
	Qiao, Yunbo 1; Wang, Zejian2,3 ; Tan, Fangzhi4 ; Chen, Jun 5,6; Lin, Jianxiang 1; Yang, Jie 3; Li, Hui 3; Wang, Xiongjun 1; Sali, Andrej 7,8; Zhang, Liye2 ; Zhong, Guisheng2,4
	2020-09-02
发表期刊	MOLECULAR THERAPY
ISSN	1525-0016
卷号	28 期号:9 页码:2083-2095
DOI	10.1016/j.ymthe.2020.05.026
摘要	Transcription growth factor beta (TGF-beta) signaling-triggered epithelial-to-mesenchymal transition (EMT) process is associated with tumor stemness, metastasis, and chemotherapy resistance. However, the epigenomic basis for TGF-beta-induced EMT remains largely unknown. Here we reveal that HDAC1-mediated global histone deacetylation and the gain of specific histone H3 lysine 27 acetylation (H3K27ac)-marked enhancers are essential for the TGF-beta-induced EMT process. Enhancers gained upon TGF-beta treatment are linked to gene activation of EMT markers and cancer metastasis. Notably, dynamic enhancer gain or loss mainly occurs within pre-existing topologically associated domains (TADs) in epithelial cells, with minimal three-dimensional (3D) genome architecture reorganization. Through motif enrichment analysis of enhancers that are lost or gained upon TGF-beta stimulation, we identify FOXA2 as a key factor to activate epithelial-specific enhancer activity, and we also find that TEAD4 forms a complex with SMAD2/3 to mediate TGF-beta signaling-triggered mesenchymal enhancer reprogramming. Together, our results implicate that key transcription-factor (TF)-mediated enhancer reprogramming modulates the developmental transition in TGF-beta signaling-associated cancer metastasis.
收录类别	SCI ; SCIE
语种	英语
资助项目	National Key Research and Development Program of China[2018YFC1004700][2016YFC0905900][2017YFC1001300][2018YFC1004602] ; National Natural Science Foundation of China[31771130][31871332][31601185][31701284] ; Excellent Youth Foundation of Guangdong Scientific Committee[2020B1515020018]
WOS研究方向	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
WOS类目	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental
WOS记录号	WOS:000571942900012
出版者	CELL PRESS
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/123582
专题	iHuman研究所_PI研究组_钟桂生组生命科学与技术学院_PI研究组_张力烨组生命科学与技术学院_博士生
共同第一作者	Wang, Zejian; Tan, Fangzhi; Chen, Jun
通讯作者	Qiao, Yunbo; Zhang, Liye; Zhong, Guisheng
作者单位	1.Guangzhou Univ, Precise Genome Engn Ctr, Sch Life Sci, Guangzhou 510006, Peoples R China; 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China; 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 4.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China; 5.Nankai Univ, State Key Lab Med Chem Biol, 94 Weijin Rd, Tianjin 300071, Peoples R China; 6.Nankai Univ, Coll Life Sci, 94 Weijin Rd, Tianjin 300071, Peoples R China; 7.Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, Dept Pharmaceut Chem, San Francisco, CA 94158 USA; 8.Univ Calif San Francisco, Calif Inst Quantitat Biosci, San Francisco, CA 94158 USA
通讯作者单位	生命科学与技术学院; iHuman研究所
推荐引用方式 GB/T 7714	Qiao, Yunbo,Wang, Zejian,Tan, Fangzhi,et al. Enhancer Reprogramming within Pre-existing Topologically Associated Domains Promotes TGF-beta-Induced EMT and Cancer Metastasis[J]. MOLECULAR THERAPY,2020,28(9):2083-2095.
APA	Qiao, Yunbo.,Wang, Zejian.,Tan, Fangzhi.,Chen, Jun.,Lin, Jianxiang.,...&Zhong, Guisheng.(2020).Enhancer Reprogramming within Pre-existing Topologically Associated Domains Promotes TGF-beta-Induced EMT and Cancer Metastasis.MOLECULAR THERAPY,28(9),2083-2095.
MLA	Qiao, Yunbo,et al."Enhancer Reprogramming within Pre-existing Topologically Associated Domains Promotes TGF-beta-Induced EMT and Cancer Metastasis".MOLECULAR THERAPY 28.9(2020):2083-2095.