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Videos de Conceptos Relacionados

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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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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Cis-regulatory Sequences02:02

Cis-regulatory Sequences

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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

General 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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RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

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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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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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Video Experimental Relacionado

Updated: May 21, 2025

High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy
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Las interacciones del factor de transcripción guiadas por el ADN extienden el código regulador del gen humano

Zhiyuan Xie1, Ilya Sokolov2,3, Maria Osmala4

  • 1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.

Nature
|April 9, 2025
PubMed
Resumen

Los investigadores mapearon las interacciones entre los factores de transcripción humanos (TF) para comprender el código regulador del gen. Identificaron miles de interacciones TF-TF y nuevos motivos compuestos, revelando ideas sobre el destino y el desarrollo celular.

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Last Updated: May 21, 2025

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Área de la Ciencia:

  • La genómica
  • Biología molecular
  • Biología de sistemas

Sus antecedentes:

  • Los factores de transcripción (TF) que se unen al ADN forman el código regulador genético, crucial para el destino celular y los programas de transcripción.
  • La regulación genética humana es compleja, involucrando a más de 1.600 TFs que interactúan, pero el paisaje de sus interacciones ligadas al ADN sigue estando mal definido.

Objetivo del estudio:

  • Mapear las interacciones bioquímicas entre los factores de transcripción humanos vinculados al ADN.
  • Identificar las preferencias de unión TF-TF, las interacciones y las secuencias de ADN unidas simultáneamente.
  • Descubrir nuevos motivos compuestos formados por pares de TF que interactúan.

Principales métodos:

  • Se utilizó CAP-SELEX (Procesamiento de matrices celulares - Evolución sistemática de los ligandos por enriquecimiento exponencial), un método de alto rendimiento.
  • Se examinaron más de 58.000 pares de factor de transcripción-factor de transcripción para identificar los pares que interactúan y sus preferencias de unión al ADN.

Principales resultados:

  • Se identificaron 2.198 pares de TF que interactúan, de los cuales 1.329 muestran un vínculo preferencial con arreglos de motivos específicos.
  • Descubrió 1.131 nuevos motivos compuestos TF-TF, distintos de los motivos TF individuales.
  • Se estima que la pantalla identificó entre el 18% y el 47% de todos los motivos humanos de TF-TF.

Conclusiones:

  • Los nuevos motivos compuestos están enriquecidos con elementos específicos del tipo de célula, son activos in vivo y a menudo se forman entre TFs coexpresadas en el desarrollo.
  • Las interacciones entre los TF que definen los ejes embrionarios explican cómo los TF similares pueden especificar tipos de células distintos a lo largo de estos ejes.