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Related Concept Videos

Regulation of Expression Occurs at Multiple Steps02:24

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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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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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Cis-regulatory Sequences02:02

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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
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Related Experiment Video

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Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
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Expression pattern determines regulatory logic.

Carlos Mora-Martinez1

  • 1Evo-devo Helsinki community, Centre of Excellence in Experimental and Computational Developmental Biology, Institute of Biotechnology, University of Helsinki, Helsinki, Finland.

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|January 4, 2021
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Summary

This study developed computational gene regulatory networks (GRNs) to model cell differentiation. Broadly expressed genes show redundant regulation and distinct cis-regulatory module architecture, explaining their resilience to mutations.

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Area of Science:

  • Computational biology
  • Developmental biology
  • Systems biology

Background:

  • Understanding how a single genome specifies numerous cell types is a major challenge.
  • Cell-specific gene expression is crucial for terminal differentiation.
  • Gene regulation differs between broadly expressed and cell-specific genes.

Purpose of the Study:

  • To computationally model gene regulatory networks (GRNs) that drive cell-specific expression patterns.
  • To investigate the regulatory differences between broadly expressed and cell-specific genes.
  • To hypothesize on the resilience of broadly expressed genes to mutations.

Main Methods:

  • In silico evolutionary strategy to generate GRNs.
  • Thermodynamic model of gene expression dynamics.
  • Incorporation of DNA sequences, transcription factor matrices, and chromatin accessibility.

Main Results:

  • Evolved GRNs mimic cell-specific gene expression and terminal differentiation.
  • Broadly expressed genes exhibit redundant regulation and distinct cis-regulatory module architecture.
  • Topological differences in GRNs explain the resilience of broadly expressed genes to mutations.

Conclusions:

  • Redundant regulation of broadly expressed genes provides robustness against mutations.
  • Findings offer insights into gene regulation phenomena like ChIP-seq HOT regions.
  • The study provides a computational framework for understanding cell differentiation and gene regulation.