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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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Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

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Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
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Co-activators and Co-repressors02:04

Co-activators and Co-repressors

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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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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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Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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Conserved Binding Sites01:49

Conserved Binding Sites

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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.
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...
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Video Experimental Relacionado

Updated: Jan 14, 2026

High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy
06:38

High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy

Published on: February 7, 2019

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baal-nf identifica variantes disruptoras de motivos que disminuyen la afinidad de unión del factor de transcripción

Breeshey Roskams-Hieter1,2, Øyvind Almelid3, Chris P Ponting4

  • 1Institute of Genetics and Cancer, MRC Human Genetics Unit, Western General Hospital, University of Edinburgh, Edinburgh, EH4 2XU, UK. b.j.roskams-hieter@sms.ed.ac.uk.

Genome biology
|January 12, 2026
PubMed
Resumen
Este resumen es generado por máquina.

Los investigadores identificaron 1.935 variantes genéticas que pueden alterar los rasgos humanos al cambiar la unión del factor de transcripción. Este descubrimiento ayuda a comprender la base genética de la variación humana.

Palabras clave:
unión específica de alelosdesequilibrio alélicoChIP-sequencingmotivosfactores de transcripción

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Área de la Ciencia:

  • Genética
  • Genómica
  • Biología Molecular

Sus antecedentes:

  • Los rasgos humanos exhiben variación genética, en parte debido a cambios en la afinidad de unión del factor de transcripción dentro de las regiones reguladoras de genes.
  • La identificación de variantes causales de rasgos específicas y sus mecanismos sigue siendo un desafío en genética.

Objetivo del estudio:

  • Identificar y proponer variantes candidatas que alteran causalmente los rasgos humanos.
  • Desarrollar un método para investigar la variación de rasgos vinculada a la alteración de la unión del factor de transcripción.

Principales métodos:

  • Utilizó baal-nf, una herramienta computacional, para analizar datos de secuenciación de inmunoprecipitación de cromatina.
  • Identificó sitios de unión alélica en loci heterocigotos dentro de los motivos de unión de factores de transcripción y cofactores.
  • Se centró en posiciones concordantes de afinidad para identificar variantes funcionales.

Principales resultados:

  • Propuso 1.935 variantes como fuertes candidatas para alterar causalmente los rasgos humanos.
  • Demostró que estos sitios de unión alélica identificados se conservan evolutivamente.
  • Mostró el enriquecimiento de estos sitios para asociaciones con rasgos humanos y expresión génica.

Conclusiones:

  • El método baal-nf identifica eficazmente sitios de unión alélica de alta calidad.
  • Estos hallazgos proporcionan un recurso valioso para estudiar los fundamentos genéticos de la variación de rasgos humanos.
  • La alteración de la unión del factor de transcripción es un mecanismo importante que contribuye a la diversidad de rasgos humanos.