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Related Concept Videos

Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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 addition of a...
Proteins: From Genes to Degradation02:11

Proteins: From Genes to Degradation

Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick.  Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA molecules by RNA...
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

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.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

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.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Mutations01:39

Mutations

Overview
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...

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Genetic noise control via protein oligomerization.

Cheol-Min Ghim1, Eivind Almaas

  • 1Microbial Systems Biology Group, Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, 7000 East Avenue Livermore, CA 94550, USA. ghim1@llnl.gov

BMC Systems Biology
|November 5, 2008
PubMed
Summary

Protein dimerization significantly reduces molecular noise in gene expression, shifting it to high frequencies. This stabilization enhances the robustness of genetic circuits and bistable switches, with implications for synthetic biology and organism fitness.

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Area of Science:

  • Systems Biology
  • Molecular Biology
  • Biophysics

Background:

  • Cellular gene expression involves random events across different timescales, leading to molecular noise.
  • This noise impacts cellular signaling, phenotype, and population dynamics.
  • While network architecture's role in noise tolerance is studied, protein-protein interactions' dynamic role is less understood.

Purpose of the Study:

  • To develop a stochastic model for gene regulation incorporating protein-protein interactions.
  • To investigate the dynamic role of protein dimerization in modulating molecular noise.
  • To assess the impact of dimerization on gene expression noise and switch stability.

Main Methods:

  • Developed a fully stochastic model for single-gene positive feedback and a two-gene toggle switch.
  • Integrated quantitative in vivo and in vitro data.
  • Explicitly modeled fast binding-unbinding kinetics of proteins, RNA polymerases, and DNA sequences.

Main Results:

  • Protein dimerization reduces overall noise levels and shifts noise frequency to high-frequency regimes.
  • This effect is independent of transcription factor type (monomer/dimer) and model topology.
  • Dimerization significantly reduces random switching rates in toggle switches, enhancing bistable state stability.

Conclusions:

  • Protein binding acts as a buffer against fluctuations in genetic activity.
  • Protein oligomerization offers a rapid mechanism for noise control without additional protein expression.
  • Stabilized regulatory circuits and epigenetic memory have implications for organism fitness and synthetic biology.