Location of Repository

The Role of Input Noise in Transcriptional Regulation

By Gašper Tkačik, Thomas Gregor and William Bialek


Gene expression levels fluctuate even under constant external conditions. Much emphasis has usually been placed on the components of this noise that are due to randomness in transcription and translation. Here we focus on the role of noise associated with the inputs to transcriptional regulation; in particular, we analyze the effects of random arrival times and binding of transcription factors to their target sites along the genome. This contribution to the total noise sets a fundamental physical limit to the reliability of genetic control, and has clear signatures, but we show that these are easily obscured by experimental limitations and even by conventional methods for plotting the variance vs. mean expression level. We argue that simple, universal models of noise dominated by transcription and translation are inconsistent with the embedding of gene expression in a network of regulatory interactions. Analysis of recent experiments on transcriptional control in the early Drosophila embryo shows that these results are quantitatively consistent with the predicted signatures of input noise, and we discuss the experiments needed to test the importance of input noise more generally

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:2475664
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles



    1. (1992). A Genetic Switch. Second edition: Phage l and Higher Organisms Cell Press: Cambridge,
    2. (1999). Characterization of the DNA binding properties of the bHLH domain of Deadpan to single and tandem sites,
    3. (2004). Control of stochasticity in eukaryotic gene expression. Science 304: 1811–1814.
    4. (1998). Cooperative DNA– binding by Bicoid provides a mechanism for threshold dependent gene activation in the Drosophila embryo.
    5. (2006). Cooperativity, sensitivity and noise in biochemical signaling.
    6. (1981). Critical limiting factors in the design of the eye and visual cortex.
    7. (1943). Delbru ¨ck M
    8. (2007). Developmental biology: A ten per cent solution.
    9. (1942). Energy, quanta, and vision.
    10. (1965). Fluctuation in membrane potential of axons and the problem of coding.
    11. (1968). Fluctuation phenomena in nerve membrane.
    12. (1972). Inferences about membrane properties from electrical noise measurement.
    13. (2002). Intrinsic and extrinsic contributions to stochasticity in gene expression.
    14. (1998). Ion channel stochasticity may be critical in determining the reliability and precision of spike timing.
    15. (2003). Noise in eukaryotic gene expression.
    16. (2006). Noise in protein expression scales with natural protein abundance.
    17. (2002). Oudenaarden A
    18. (2005). Physical limits to biochemical signaling.
    19. (1987). Physical limits to sensation and perception.
    20. (1977). Physics of chemoreception.
    21. (1975). Potassium and sodium ion current noise in the membrane of the squid giant axon.
    22. (2007). Probing the limits to positional information.
    23. (2005). Real–time kinetics of gene activity in individual bacteria.
    24. (1971). Responses to single quanta of light in the retinal ganglion cells of the cat.
    25. (2005). Self–consistent proteomic field theory of stochastic gene switches.
    26. (2006). Single–cell proteomic analysis of S cerevisiae reveals the architecture of biological noise.
    27. (1977). Sodium channels in nerve apparently have two conductance states.
    28. (1950). Some observations on biological noise.
    29. (1952). Spontaneous subthreshold activity at motor nerve endings.
    30. (2007). Stability and nuclear dynamics of the Bicoid morphogen gradient.
    31. (2002). Stochastic gene expression in a single cell.
    32. (2004). Summing up the noise in gene networks.
    33. (2006). ten Wolde PR
    34. (2002). The activity of the Drosophila morphogenetic protein Bicoid is inhibited by a domain located outside its homeodomain,
    35. (1996). The single Cys2–His2 zinc finger domain of the GAGA protein flanked by basic residues is sufficient for high–affinity specific DNA binding,
    36. (1980). The variance of sodium current fluctuations at the node of Ranvier.
    37. (1971). Theory of threshold fluctuations in nerves. I: Relationships between electrical noise and fluctuations in axon firing.
    38. (1971). Theory of threshold fluctuations in nerves. II: Analysis of various sources of membrane noise.
    39. (2002). Thinking about the brain. In Physics of Biomolecules and Cells: Les Houches Session
    40. (2005). Ultrasensitivity and noise propagation in a synthetic transcriptional cascade.
    41. (2005). van Oudenaarden A

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.