Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2019; 10:7185-7186.

Loss of ZNF32 augments the regeneration of nervous lateral line system through negative regulation of SOX2 transcription

Yuyan Wei, Kai Li, Shaohua Yao, Junping Gao, Jun Li, Yanna Shang, Jie Zhang, Le Zhang, Yanyan Li, Xianming Mo, Wentong Meng, Rong Xiang, Jiankun Hu, Ping Lin _ and Yuquan Wei

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Oncotarget. 2016; 7:70420-70436. https://doi.org/10.18632/oncotarget.11895

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Abstract

Yuyan Wei1, Kai Li1, Shaohua Yao2, Junping Gao1, Jun Li1, Yanna Shang3, Jie Zhang1, Le Zhang1, Yanyan Li1, Xianming Mo3, Wentong Meng3, Rong Xiang5, Jiankun Hu4, Ping Lin1, Yuquan Wei2

1Division of Experimental Oncology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China

2Division of Cancer Biotherapy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China

3Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China

4Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China

5Department of clinical medicine, School of Medicine, Nankai University and Collaborative Innovation Center for Biotherapy, Tianjin, P.R. China

Correspondence to:

Ping Lin, email: linping@scu.edu.cn

Jiankun Hu, email: hujkwch@126.com

Keywords: ZNF32, SOX2, regeneration, DNA binding site, NLS

Received: December 02, 2015     Accepted: August 27, 2016     Published: September 08, 2016

ABSTRACT

Human zinc finger protein 32 (ZNF32) is a Cys2-His2 zinc-finger transcription factor that plays an important role in cell fate, yet much of its function remains unknown. Here, we reveal that the zebrafish ZNF32 homologue zfZNF32 is expressed in the nervous system, particularly in the lateral line system. ZfZNF32 knock-out zebrafish (zfZNF-/-) were generated using the CRISPR-associated protein 9 system. We found that the regenerative capacity of the lateral line system was increased in zfZNF-/- upon hair cell damage compared with the wild type. Moreover, SOX2 was essential for the zfZNF32-dependent modulation of lateral line system regeneration. Mechanistic studies showed that ZNF32 suppressed SOX2 transcription by directly binding to a consensus sequence (5’-gcattt-3’) in the SOX2 promoter. In addition, ZNF32 localizes to the nucleus, and we have identified that amino acids 1-169 (Aa 1-169) and each of three independent nuclear localization signals (NLSs) in ZNF32 are indispensable for ZNF32 nuclear trafficking. Mutating the NLSs disrupted the inhibitory effect of ZNF32 in SOX2 expression, highlighting the critical role of the NLSs in ZNF32 function. Our findings reveal a pivotal role for ZNF32 function in SOX2 expression and regeneration regulation.


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