In vivo tests of thermodynamic models of transcription repressor function

In vivo tests of thermodynamic models of transcription repressor function
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DOI:
10.1016/j.bpc.2011.06.005
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发表时间:
2011-11-01
影响因子:
3.8
通讯作者:
Beckett, Dorothy
Beckett, Dorothy
中科院分区:
生物学4区
文献类型:
--
作者:
Tungtur, Sudheer;Skinner, Harlyn;Beckett, Dorothy

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One emphasis of the Gibbs Conference on Biothermodynamics is the value of thermodynamic measurements for understanding behaviors of biological systems. In this study, the correlation between thermodynamic measurements of in vitro DNA binding affinity with in vivo transcription repression was investigated for two transcription repressors. In the first system, which comprised an engineered LacI/GalR homolog, mutational changes altered the equilibrium constant for binding DNA. Changes correlated with altered repression, but estimates of in vivo repressor concentration suggest a >= 25-fold discrepancy with in vitro conditions. In the second system, changes in ligand binding to BirA altered dimerization and subsequent DNA occupancy. Again, these changes correlate with altered in vivo repression, but comparison with in vitro measurements reveals a similar to 10-fold discrepancy. Further analysis of each system suggests that the observed discrepancies between in vitro and in vivo results reflect the contributions of additional equilibria to the transcription repression process. (C) 2011 Elsevier B.V. All rights reserved.