机构：[1]Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.[2]State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.[3]Laboratory of Animal Sciences Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, National Institutes of Health, Frederick, MD, USA.[4]Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA
The Hippo TEAD-transcriptional regulators YAP1 and TAZ are central for cell renewal and cancer growth; however, the specific downstream gene networks involved in their activity are not completely understood. Here we introduce TEADi, a genetically encoded inhibitor of the interaction of YAP1 and TAZ with TEAD, as a tool to characterize the transcriptional networks and biological effects regulated by TEAD transcription factors. Blockage of TEAD activity by TEADi in human keratinocytes and mouse skin leads to reduced proliferation and rapid activation of differentiation programs. Analysis of gene networks affected by TEADi and YAP1/TAZ knockdown identifies KLF4 as a central transcriptional node regulated by YAP1/TAZ-TEAD in keratinocyte differentiation. Moreover, we show that TEAD and KLF4 can regulate the activity of each other, indicating that these factors are part of a transcriptional regulatory loop. Our study establishes TEADi as a resource for studying YAP1/TAZ-TEAD dependent effects.
基金：
This research was supported by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer Research (ZIA BC
011764 and ZIA BC 011763). Yao Yuan and Qianming Chen were supported by grants
from the National Natural Science Foundation of China (81520108009, 81621062), and
111 Project of MOE (B14038), China.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
最新[2023]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
第一作者：
第一作者机构：[1]Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.[2]State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
通讯作者：
推荐引用方式(GB/T 7714)：
Yao Yuan,Jeannie Park,Amber Feng,et al.YAP1/TAZ-TEAD transcriptional networks maintain skin homeostasis by regulating cell proliferation and limiting KLF4 activity.[J].Nature communications.2020,11(1):1472.doi:10.1038/s41467-020-15301-0.
APA：
Yao Yuan,Jeannie Park,Amber Feng,Parirokh Awasthi,Zhiyong Wang...&Ramiro Iglesias-Bartolome.(2020).YAP1/TAZ-TEAD transcriptional networks maintain skin homeostasis by regulating cell proliferation and limiting KLF4 activity..Nature communications,11,(1)
MLA：
Yao Yuan,et al."YAP1/TAZ-TEAD transcriptional networks maintain skin homeostasis by regulating cell proliferation and limiting KLF4 activity.".Nature communications 11..1(2020):1472
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