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Related Concept Videos

Cis-regulatory Sequences02:02

Cis-regulatory Sequences

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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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Pulse regulation involves physiological mechanisms that ensure adequate blood flow throughout the body. The heartbeat, regulated by the autonomic nervous system, is influenced by hormonal balance, physical activity, and emotional state.
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The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
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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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The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences.  The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
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Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
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Quantitative Comparison of cis-Regulatory Element CRE Activities in Transgenic Drosophila melanogaster
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Differences in evolutionary accessibility determine which equally effective regulatory motif evolves to generate

Kun Xiong1,2, Mark Gerstein2,3,4,5, Joanna Masel6

  • 1Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA.

Genetics
|November 5, 2021
PubMed
Summary

Evolutionary accessibility, not just optimal function, shapes transcriptional regulatory network motifs. Incoherent feed-forward loops often evolve before negative feedback loops, influenced by gene expression levels.

Keywords:
adaptationismgene regulatory networkmutation-biased adaptationpulse generationtranscriptional regulation

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Area of Science:

  • Systems Biology
  • Evolutionary Biology
  • Computational Biology

Background:

  • Transcriptional regulatory networks (TRNs) feature recurring motifs, often explained by adaptation and optimal function.
  • However, the ease of evolution for certain motifs may also influence their prevalence.

Purpose of the Study:

  • To investigate the evolutionary dynamics of TRN motifs computationally.
  • To compare the evolutionary accessibility and performance of type 1 incoherent feed-forward loops (I1FFLs) and negative feedback loops (NFBLs) in generating a protein pulse.

Main Methods:

  • Computational evolution of TRNs to produce a specific protein pulse output.
  • Analysis of motif evolution under varying selection conditions (pulse height, response speed).

Main Results:

  • Both I1FFLs and NFBLs emerged as primary solutions, achieving similar performance.
  • I1FFLs generally evolved more frequently than NFBLs.
  • Selection for pulse speed favored I1FFLs, while selection for pulse height favored NFBLs.
  • I1FFLs were more evolutionarily accessible early in the process; NFBLs often evolved from I1FFL-NFBL combinations.
  • In S. cerevisiae, NFBL output genes showed higher expression than I1FFL output genes.

Conclusions:

  • Evolutionary accessibility, influenced by gene expression levels, plays a critical role in shaping the prevalence of TRN motifs.
  • The observed motif usage may not solely reflect functional optimization but also the ease of their evolutionary emergence.