YAP1/TAZ-TEAD transcriptional networks maintain skin homeostasis by regulating cell proliferation and limiting KLF4 activity

Yao Yuan, Jeannie Park, Amber Feng, Parirokh Awasthi, Zhiyong Wang, Qianming Chen and Ramiro Iglesias-Bartolome ()
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Yao Yuan: National Cancer Institute, National Institutes of Health
Jeannie Park: National Cancer Institute, National Institutes of Health
Amber Feng: National Cancer Institute, National Institutes of Health
Parirokh Awasthi: Frederick National Laboratory for Cancer Research, National Institutes of Health
Zhiyong Wang: Sichuan University
Qianming Chen: Sichuan University
Ramiro Iglesias-Bartolome: National Cancer Institute, National Institutes of Health

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-15301-0

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