The authors regret that following the publication of the original article,the authors noticed that Funds in Acknowledgements section was incorrect,in which a fund(No.2020YFA0906903)supporting most of experimental resu...The authors regret that following the publication of the original article,the authors noticed that Funds in Acknowledgements section was incorrect,in which a fund(No.2020YFA0906903)supporting most of experimental results of Dr.Xinmao Chen was missed by us.We sincerely apologize again for the oversight and appreciate your understanding in allowing us to correct this matter.展开更多
Cooperative activation is critical for the applications of synthetic biology in mammalian cells.In this study,we have developed cooperative transcription factor by fusing oligomerization domain in mammalian cells.Firs...Cooperative activation is critical for the applications of synthetic biology in mammalian cells.In this study,we have developed cooperative transcription factor by fusing oligomerization domain in mammalian cells.Firstly,we demonstrated that two oligomerized domains(CI434 and CI)successfully improved transcription factor cooperativity in bacterial cells but failed to increase cooperativity in mammalian cells,possibly because the additional mammalian activation domain disrupted their oligomerization capability.Therefore,we chose a different type of oligomerized domain(CarHC),whose ability to oligomerize is not dependent on its C-terminal domains,to fuse with a transcription factor(RpaR)and activation domain(VTR3),forming a potential cooperative transcription activator RpaR-CarH-VTR3 for mammalian regulatory systems.Compared with RpaR-VTR3,the cooperativity of RpaR-CarH-VTR3 was significantly improved with higher Hill coefficient and a narrower input range in the inducible switch system in mammalian cells.Moreover,a mathematical model based on statistical mechanics model was developed and the simulation results supported the hypothesis that the tetramer of the CarH domain in mammalian cells was the reason for the cooperative capacity of RpaR-CarH-VTR3.展开更多
文摘The authors regret that following the publication of the original article,the authors noticed that Funds in Acknowledgements section was incorrect,in which a fund(No.2020YFA0906903)supporting most of experimental results of Dr.Xinmao Chen was missed by us.We sincerely apologize again for the oversight and appreciate your understanding in allowing us to correct this matter.
基金supported by Ministry of Science and Technology of China [No.2021YFA0910700,2021YFF1200500,2020YFA0907101]the Natural Science Foundation of China [No.12090050,12090054,32071412]+1 种基金the Chinese Academy of Sciences [No.QYZDB-SSW-SMC050]CAS Youth Interdisciplinary Team and the Shenzhen Science and Technology Innovation Committee [No.JCYJ20180507182241844,JCHZ20200005,DWKF20190009].
文摘Cooperative activation is critical for the applications of synthetic biology in mammalian cells.In this study,we have developed cooperative transcription factor by fusing oligomerization domain in mammalian cells.Firstly,we demonstrated that two oligomerized domains(CI434 and CI)successfully improved transcription factor cooperativity in bacterial cells but failed to increase cooperativity in mammalian cells,possibly because the additional mammalian activation domain disrupted their oligomerization capability.Therefore,we chose a different type of oligomerized domain(CarHC),whose ability to oligomerize is not dependent on its C-terminal domains,to fuse with a transcription factor(RpaR)and activation domain(VTR3),forming a potential cooperative transcription activator RpaR-CarH-VTR3 for mammalian regulatory systems.Compared with RpaR-VTR3,the cooperativity of RpaR-CarH-VTR3 was significantly improved with higher Hill coefficient and a narrower input range in the inducible switch system in mammalian cells.Moreover,a mathematical model based on statistical mechanics model was developed and the simulation results supported the hypothesis that the tetramer of the CarH domain in mammalian cells was the reason for the cooperative capacity of RpaR-CarH-VTR3.