RETRACTED ARTICLE: REST regulates the cell cycle for cardiac development and regeneration

Donghong Zhang, Yidong Wang, Pengfei Lu, Ping Wang, Xinchun Yuan, Jianyun Yan, Chenleng Cai, Ching-Pin Chang, Deyou Zheng, Bingruo Wu and Bin Zhou ()
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Donghong Zhang: Albert Einstein College of Medicine
Yidong Wang: Albert Einstein College of Medicine
Pengfei Lu: Albert Einstein College of Medicine
Ping Wang: Albert Einstein College of Medicine
Xinchun Yuan: The First Affiliated Hospital of Nanchang University
Jianyun Yan: Icahn School of Medicine at Mount Sinai
Chenleng Cai: Icahn School of Medicine at Mount Sinai
Ching-Pin Chang: Indian University School of Medicine
Deyou Zheng: Albert Einstein College of Medicine
Bingruo Wu: Albert Einstein College of Medicine
Bin Zhou: Albert Einstein College of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract Despite the importance of cardiomyocyte proliferation in cardiac development and regeneration, the mechanisms that promote cardiomyocyte cell cycle remain incompletely understood. RE1 silencing transcription factor (REST) is a transcriptional repressor of neuronal genes. Here we show that REST also regulates the cardiomyocyte cell cycle. REST binds and represses the cell cycle inhibitor gene p21 and is required for mouse cardiac development and regeneration. Rest deletion de-represses p21 and inhibits the cardiomyocyte cell cycle and proliferation in embryonic or regenerating hearts. By contrast, REST overexpression in cultured cardiomyocytes represses p21 and increases proliferation. We further show that p21 knockout rescues cardiomyocyte cell cycle and proliferation defects resulting from Rest deletion. Our study reveals a REST-p21 regulatory axis as a mechanism for cell cycle progression in cardiomyocytes, which might be exploited therapeutically to enhance cardiac regeneration.

Date: 2017
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DOI: 10.1038/s41467-017-02210-y

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