期刊
MOLECULAR CELL
卷 37, 期 3, 页码 418-428出版社
CELL PRESS
DOI: 10.1016/j.molcel.2010.01.016
关键词
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资金
- Human Frontier Science Program (HFSP) [RGY0085/2005-C]
- European Commission (EC) [TRANS-TAR]
- FP7 Model-In
- AIRC (Italian Association for Research on Cancer)
- Italian Institute of Technology (IIT)
A paradigm in transcriptional regulation is that graded increases in transcription factor (TF) concentration are translated into on/off transcriptional responses by cooperative TF binding to adjacent sites. Digital transcriptional responses underlie the definition of anatomical boundaries during development. Here we show that NF-kappa B, a TF controlling inflammation and immunity, is conversely an analog transcriptional regulator that uses clustered binding sites noncooperatively. We observed that increasing concentrations of NF-kappa B are translated into gradual increments in gene transcription. We provide a thermodynamic interpretation of the experimental observations by combining quantitative measurements and a minimal physical model of an NF-kappa B-dependent promoter. We demonstrate that NF-kappa B binds independently to adjacent sites to promote additive RNA Pol II recruitment and graded transcriptional outputs. These findings reveal an alternative mode of operation of clustered TF binding sites, which might function in biological conditions where the transcriptional output is proportional to the strength of an environmental input.
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