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Related Concept Videos

Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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 dimers that...
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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 dimers that...
General Transcription Factors01:30

General Transcription Factors

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...
Conserved Binding Sites01:49

Conserved Binding Sites

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.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Conserved Binding Sites01:49

Conserved Binding Sites

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.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

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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HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
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Published on: March 31, 2019

Cofactor binding evokes latent differences in DNA binding specificity between Hox proteins.

Matthew Slattery1, Todd Riley, Peng Liu

  • 1Department of Biochemistry and Molecular Biophysics, Columbia University, 701 West 168(th) Street, HHSC 1104, New York, NY 10032, USA.

Cell
|December 14, 2011
PubMed
Summary
This summary is machine-generated.

Transcription factors gain new DNA binding abilities when forming complexes with cofactors. This study reveals how Drosophila Hox proteins change recognition properties with the Extradenticle-Homothorax cofactor.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Transcription factor families share DNA binding similarities but have distinct in vivo functions.
  • Transcription factors often bind DNA as multiprotein complexes, suggesting altered DNA binding specificities.

Purpose of the Study:

  • To investigate if transcription factor complex formation modifies DNA binding specificities.
  • To develop a method for determining DNA sequence affinities of transcription factor complexes.

Main Methods:

  • Developed SELEX-seq, an experimental and computational platform.
  • Applied SELEX-seq to all eight Drosophila Hox proteins and the Extradenticle-Homothorax (Exd) cofactor.

Main Results:

  • Drosophila Hox proteins exhibit novel DNA recognition properties when complexed with Exd.
  • Exd-Hox specificities fall into three classes, aligning with Hox gene collinearity.
  • DNA structure predictions indicate distinct minor groove topography preferences for anterior and posterior Hox proteins.

Conclusions:

  • Cofactor interactions, like Exd with Hox proteins, lead to emergent DNA recognition properties.
  • These emergent properties contribute to the in vivo specificity of transcription factors.