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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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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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In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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Macromolecular Crowding Regulates the Gene Expression Profile by Limiting Diffusion.

Mahdi Golkaram1, Stefan Hellander2, Brian Drawert2

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Macromolecular crowding enhances gene expression robustness by limiting transcription factor diffusion, leading to more homogeneous cell populations. Larger crowding molecules are more effective at noise reduction.

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Area of Science:

  • Cellular biology
  • Biophysics
  • Systems biology

Background:

  • Gene expression exhibits stochasticity, causing cell population heterogeneity.
  • Macromolecular crowding is increasingly recognized for its functional roles in cellular processes.

Purpose of the Study:

  • To elucidate the role of macromolecular crowding in transcription and translation.
  • To investigate how macromolecular crowding influences gene expression noise and cell homogeneity.

Main Methods:

  • Development of a spatial stochastic model.
  • Simulation of gene expression dynamics under varying crowding conditions.

Main Results:

  • Macromolecular crowding reduces gene expression noise, measured by mRNA distribution kurtosis.
  • Crowding limits transcription factor diffusion, eliminating unstable intermediate states.
  • Larger crowding molecules reduce noise more effectively than smaller ones.
  • Local chromatin density variations and nuclear volume exclusion contribute to cell population homogeneity.

Conclusions:

  • Macromolecular crowding promotes gene expression robustness and cellular homogeneity.
  • The biophysical effects of crowding are critical for regulating gene expression noise.
  • Chromatin organization within the nucleus plays a significant role in achieving homogeneous cell populations.