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Related Concept Videos

Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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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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Transcription Factors02:16

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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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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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General Transcription Factors01:30

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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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Conserved Binding Sites01:49

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Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy
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A deterministic code for transcription factor-DNA recognition through computation of binding interfaces.

Marco Trerotola1, Laura Antolini2, Laura Beni1

  • 1Laboratory of Cancer Pathology, Center for Advanced Studies and Technology (CAST), University "G. D' Annunzio", Via L. Polacchi 11, 66100 Chieti, Italy.

NAR Genomics and Bioinformatics
|March 9, 2022
PubMed
Summary
This summary is machine-generated.

Researchers identified a DNA recognition code between transcription factor (TF) amino acids and DNA bases. This structural and mutagenesis code reveals fundamental rules governing gene expression regulation.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • The precise mechanisms dictating transcription factor (TF) binding specificity to DNA remain incompletely understood.
  • Identifying the rules governing TF-DNA interactions is crucial for understanding gene regulation.

Purpose of the Study:

  • To elucidate the determinants of transcription factor amino acid-DNA base binding selectivity.
  • To establish fundamental rules for TF-DNA recognition.

Main Methods:

  • Analysis of crystal structures of TF-DNA complexes to identify the 'structural code'.
  • Meta-analysis of random-mutagenesis studies on Zinc finger proteins to identify the 'mutagenesis code'.
  • Comparative analysis of the structural and mutagenesis codes.

Main Results:

  • High-frequency interactions between TF amino acid side chains and DNA bases were identified, forming the 'structural code'.
  • Similar selective interactions were found for mutagenized residues, constituting the 'mutagenesis code'.
  • The structural and mutagenesis codes demonstrated a high degree of concordance (P = 3.1 x 10^-33), validating fundamental TF-DNA binding rules.
  • Geometry-dictated residue selection was observed in TFs with overlapping specificities.

Conclusions:

  • A DNA recognition code based on the physical-chemical properties of interacting residues has been identified.
  • This discovery advances the understanding of gene expression regulation and TF-DNA interactions.
  • The findings provide a foundation for integrating these rules into more complex models of gene regulation.