REST regulates the cell cycle for cardiac development and regeneration.
REST regulates the cell cycle for cardiac development and regeneration.
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DOI：
10.1038/s41467-017-02210-y
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发表时间：
2017-12-07
影响因子：
16.6
通讯作者：
Zhou B
中科院分区：
文献类型：
--
作者：
Zhang D;Wang Y;Lu P;Wang P;Yuan X;Yan J;Cai C;Chang CP;Zheng D;Wu B;Zhou B
尽管心肌细胞增殖在心脏发育和再生中的重要性，但促进心肌细胞周期的机制仍不完全清楚。RE1沉默转录因子(REST)是神经元基因的转录抑制因子。在这里，我们展示了REST也调节心肌细胞周期。REST结合并抑制细胞周期抑制基因p21，是小鼠心脏发育和再生所必需的。REST缺失抑制了p21的表达，抑制了胚胎或再生心脏的心肌细胞周期和增殖。相比之下，培养的心肌细胞中REST的过度表达抑制了p21并促进了增殖。我们进一步证明，p21基因敲除可以挽救因REST缺失而导致的心肌细胞周期和增殖缺陷。我们的研究揭示了Rest-p21调节轴作为心肌细胞细胞周期进展的一种机制，这可能被用于治疗以促进心脏再生。在发育和心脏再生过程中调控心肌细胞增殖的机制还不完全清楚。作者表明，转录因子REST通过结合和抑制细胞周期抑制物p21来调节心肌细胞的增殖。
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. The mechanisms regulating cardiomyocyte proliferation during development and cardiac regeneration are incompletely understood. The authors show that the transcription factor REST regulates cardiomyocyte proliferation by binding and repressing the cell cycle inhibitor p21.
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DOI：
10.1126/science.1199010
发表时间：
2011-04-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Heallen T;Zhang M;Wang J;Bonilla-Claudio M;Klysik E;Johnson RL;Martin JF
通讯作者：
Martin JF
影响因子：
64.8
作者：
通讯作者：
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影响因子：
21.3
作者：
D'Uva, Gabriele;Aharonov, Alla;Tzahor, Eldad
通讯作者：
Tzahor, Eldad
DOI：
10.1073/pnas.1208863110
发表时间：
2013-01-02
影响因子：
11.1
作者：
Porrello, Enzo R.;Mahmoud, Ahmed I.;Sadek, Hesham A.
通讯作者：
Sadek, Hesham A.
影响因子：
64.8
作者：
通讯作者：
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