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Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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Noise facilitates transcriptional control under dynamic inputs.

Ryan A Kellogg1, Savaş Tay1

  • 1Department of Biosystems Science and Engineering, ETH Zürich 4058, Switzerland.

Cell
|January 31, 2015
PubMed
Summary

Cells synchronize with oscillating signals, boosting gene expression. Biochemical noise enhances this cellular response, enabling efficient information processing in dynamic environments.

Area of Science:

  • Cellular biology
  • Systems biology
  • Biophysics

Background:

  • Cells operate in complex signaling environments with time-varying inputs.
  • Understanding cellular information processing and gene expression is crucial.

Purpose of the Study:

  • Investigate how signaling networks, specifically the NF-κB pathway, process dynamic inputs.
  • Determine the role of noise in cellular information processing and gene expression.

Main Methods:

  • Utilized microfluidic single-cell measurements.
  • Employed stochastic modeling of the NF-κB pathway.
  • Studied responses to periodic cytokine (TNF) inputs.

Main Results:

  • NF-κB dynamics in fibroblasts synchronize and entrain with oscillating TNF signals.

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  • Entrainment significantly increased NF-κB oscillation amplitude and mRNA output.
  • Intrinsic biochemical noise enhances NF-κB oscillation and entrainment.
  • Cell-to-cell variability in NF-κB natural frequency provides population robustness.
  • Cells achieved entrainment over a wider range of dynamic input periods.

    • Conclusions:

    • Synergy between oscillation and noise enables efficient gene expression in dynamic signaling environments.
    • Noise plays a dual role: enhancing individual cell response and promoting population-level robustness.
    • Cellular systems are optimized for processing time-varying signals through coordinated oscillation and noise.