The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Fold Change of Nuclear NF-κB Determines TNF-Induced Transcription in Single Cells
Open accessAbstract
SUMMARY In response to TNF, NF-κB enters the nucleus and promotes inflammatory and stress-responsive gene transcription. Because NF-κB deregulation is associated with many diseases, one might expect strict control of NF-κB localization. However, nuclear NF-κB levels exhibit considerable cell-to-cell variability, even in unstimulated cells. To resolve this paradox and determine how transcription-inducing signals are encoded, we quantified single-cell NF-κB translocation dynamics and transcriptional responses in the same cells. We show that TNF-induced transcription correlates best with fold-change in nuclear NF-κB, not absolute nuclear NF-κB abundance. Using computational modeling, we find that an incoherent feed-forward loop, from competition for binding to κB motifs, could provide ‘memory’ of pre-ligand state necessary for fold-change detection. Experimentally, we observed three gene-specific patterns of transcription that are recapitulated in our model by modulating competition strength alone. Fold-change detection buffers against stochastic variation in signaling molecules and explains how cells tolerate variability in NF-κB abundance and localization.
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Metadata
- Authors
- Lee, R. E. C., Walker, S. R., Savery, K., Frank, D. A., & Gaudet, S.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 53
- Issue
- 6
- Pages
- 867-879
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1968263458
- Cited by
- 231
- References
- 11
- FWCI
- 6.22
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Lee, R. E. C., Walker, S. R., Savery, K., Frank, D. A., & Gaudet, S. (2014). Fold Change of Nuclear NF-κB Determines TNF-Induced Transcription in Single Cells. Molecular Cell. https://doi.org/10.1016/j.molcel.2014.01.026
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