Pulsatile stimulation determines timing and specificity of NF-kappa B-dependent transcription
Ashall, Louise, Horton, Caroline A., Nelson, David E., Paszek, Pawel, Harper, Claire V., Sillitoe, Kate, Ryan, Sheila, Spiller, David G., Unitt, John F., Broomhead, David S., Kell, Douglas B., Rand, D. A. (David A.), See, Violaine and White, Michael R. H.. (2009) Pulsatile stimulation determines timing and specificity of NF-kappa B-dependent transcription. Science, Vol.324 (No.5924). pp. 242-246. ISSN 0036-8075Full text not available from this repository.
Official URL: http://dx.doi.org/10.1126/science.1164860
The nuclear factor kappa B (NF-kappa B) transcription factor regulates cellular stress responses and the immune response to infection. NF-kappa B activation results in oscillations in nuclear NF-kappa B abundance. To define the function of these oscillations, we treated cells with repeated short pulses of tumor necrosis factor-alpha at various intervals to mimic pulsatile inflammatory signals. At all pulse intervals that were analyzed, we observed synchronous cycles of NF-kappa B nuclear translocation. Lower frequency stimulations gave repeated full-amplitude translocations, whereas higher frequency pulses gave reduced translocation, indicating a failure to reset. Deterministic and stochastic mathematical models predicted how negative feedback loops regulate both the resetting of the system and cellular heterogeneity. Altering the stimulation intervals gave different patterns of NF-kappa B-dependent gene expression, which supports the idea that oscillation frequency has a functional role.
|Item Type:||Journal Article|
|Divisions:||Faculty of Science > Centre for Systems Biology|
|Journal or Publication Title:||Science|
|Publisher:||American Association for the Advancement of Science|
|Date:||10 April 2009|
|Number of Pages:||5|
|Page Range:||pp. 242-246|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Royal Society (Great Britain), Engineering and Physical Sciences Research Council (EPSRC), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Medical Research Council (Great Britain) (MRC), Professor John Glover Memorial Research Fellowship, European Union, Royal Society/Wolfson Merit Award, BBSRC David Phillips Research Fellowship|
|Grant number:||BBD0107481, BBF0059381, BBC0082191, BBC0071581, G0500346, EP/C544587/1, GR/S29256/01, 005137, BBC5204711|
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