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Transcription Factors02:16

Transcription Factors

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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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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High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy
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Modelling the evolution of transcription factor binding preferences in complex eukaryotes.

Antonio Rosanova1, Alberto Colliva2, Matteo Osella2

  • 1Department of Physics and INFN, Università degli Studi di Torino, via P.Giuria 1, I-10125, Turin, Italy. antonio.rosanova@unito.it.

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Summary

Transcription factors (TFs) are organized into motif families based on shared DNA binding preferences, revealing evolutionary insights into transcriptional regulation. An evolutionary model explains this organization and identifies deviations, like expanded HOX and FOX gene families.

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Area of Science:

  • Evolutionary biology
  • Genomics
  • Molecular biology

Background:

  • Transcription factors (TFs) regulate gene expression by binding to specific DNA sequences.
  • Shared evolutionary origins lead to overlapping TF binding preferences, creating 'motif families'.
  • Motif family organization reflects the evolutionary history of transcriptional regulation.

Purpose of the Study:

  • To model the evolutionary forces shaping TF motif families in the human genome.
  • To identify deviations from neutral evolutionary scenarios in TF family organization.
  • To compare TF binding redundancy across eukaryotic species and correlate it with organismal complexity.

Main Methods:

  • Developed a one-parameter Birth-Death-Innovation evolutionary model.
  • Applied the model to the human TF repertoire to analyze motif family distribution.
  • Compared TF motif family organization across different eukaryotic species.

Main Results:

  • The evolutionary model successfully explains the observed TF distribution into motif families.
  • Identified three over-expanded TF families (e.g., HOX, FOX) and singleton TFs selected against duplication.
  • Observed higher binding preference diversification in TFs with Zinc Finger domains.
  • Found increased binding redundancy with increasing organismal complexity in eukaryotes.

Conclusions:

  • Evolutionary processes, including birth, death, and innovation, shape TF binding repertoires and their organization into motif families.
  • Deviations from neutral evolution highlight specific TF families and domains with unique evolutionary trajectories.
  • TF binding redundancy is a feature that has likely increased with the complexity of eukaryotic organisms.