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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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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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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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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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Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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Updated: Jun 30, 2025

Identifying Transcription Factor Olig2 Genomic Binding Sites in Acutely Purified PDGFR&#945;+ Cells by Low-cell Chromatin Immunoprecipitation Sequencing Analysis
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Identifying Transcription Factor Olig2 Genomic Binding Sites in Acutely Purified PDGFRα+ Cells by Low-cell Chromatin Immunoprecipitation Sequencing Analysis

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Overlapping binding sites underlie TF genomic occupancy.

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    |March 18, 2024
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    Summary
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    We developed PADIT-seq to detect low-affinity transcription factor (TF)-DNA interactions, revealing how overlapping binding sites influence gene regulation in vivo. This method expands the search for noncoding variants affecting TF binding.

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    Area of Science:

    • Molecular Biology
    • Genomics
    • Epigenetics

    Background:

    • Transcription factors (TFs) regulate gene expression through sequence-specific DNA binding.
    • Current high-throughput methods struggle to detect low-affinity TF-DNA interactions crucial for gene regulation.

    Approach:

    • Developed PADIT-seq (protein affinity to DNA by in vitro transcription and RNA sequencing) to sensitively assay TF binding preferences across all 10-bp DNA sequences.
    • Applied PADIT-seq to human TFs HOXD13 and EGR1 to generate comprehensive low-affinity binding site catalogs.

    Key Points:

    • Nucleotides flanking high-affinity TF binding sites create overlapping, lower-affinity sites.
    • These extended recognition sequences modulate TF genomic occupancy in vivo.
    • TF binding sites exhibit an inherent propensity to interweave, forming these extended sites.

    Conclusions:

    • PADIT-seq offers unprecedented sensitivity for detecting TF-DNA interactions.
    • Understanding overlapping binding sites is key to deciphering TF genomic occupancy.
    • This work expands the genomic sequence space for identifying noncoding variants that impact TF binding and gene regulation.