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Combinatorial Gene Control02:33

Combinatorial Gene Control

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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
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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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The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences.  The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
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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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Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions
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Las proteínas parecidas a policombos unen el complejo PRC2 a las islas CpG

Haojie Li1, Robert Liefke2,3, Junyi Jiang1

  • 1Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing 100875, China.

Nature
|September 5, 2017
PubMed
Resumen

Las proteínas parecidas a Polycomb (PCL) son cruciales para reclutar el complejo represivo Polycomb 2 (PRC2) a las islas CpG. Este mecanismo de unión, que involucra estructuras de hélice alada, es esencial para la regulación de la transcripción y el mantenimiento de la identidad celular.

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Área de la Ciencia:

  • Epigenética y regulación de la transcripción
  • Biología de la cromatina
  • Mecanismos moleculares de silenciamiento de genes

Sus antecedentes:

  • El complejo represivo de policombos 2 (PRC2) es vital para el silenciamiento de genes, la identidad celular y la diferenciación.
  • Las proteínas tipo policombo (PCL) (por ejemplo, PHF1, MTF2, PHF19) se asocian con PRC2, modulando potencialmente su actividad o orientación genómica.
  • Los sitios de unión de PRC2 se enriquecen en regiones ricas en CpG, incluidas las islas de CpG con baja metilación del ADN, pero el mecanismo de reclutamiento sigue sin estar claro.

Objetivo del estudio:

  • Para aclarar la base estructural y el mecanismo de unión de la proteína tipo policombo (PCL) al ADN rico en CpG.
  • Determinar el papel de las proteínas PCL en el reclutamiento del complejo represivo Polycomb 2 (PRC2) a las islas CpG.
  • Comprender la contribución de las interacciones PCL-ADN a la regulación de la transcripción in vivo.

Principales métodos:

  • Determinación de la estructura cristalina de los dominios N-terminales de PHF1 y MTF2 unidos al ADN CpG y a los péptidos H3K36me3.
  • Pruebas bioquímicas para caracterizar la especificidad de la unión al ADN.
  • Evaluación del reclutamiento de PRC2 a promotores de islas CpG en células madre embrionarias de ratón.

Principales resultados:

  • Los dominios N-terminales de PHF1 y MTF2 adoptan una estructura de hélice alada que reconoce específicamente los motivos CpG no metilados.
  • Este mecanismo de unión al ADN difiere significativamente de los motivos de hélice alada canónicos.
  • Las proteínas PCL son esenciales para el reclutamiento eficiente de PRC2 a promotores de islas CpG en células madre embrionarias de ratón.

Conclusiones:

  • Las proteínas PCL se unen directamente a los motivos CpG no metilados a través de una nueva estructura de hélice alada.
  • Las proteínas PCL juegan un papel crítico en la orientación de PRC2 a las islas CpG, un mecanismo regulador epigenético clave.
  • Este estudio proporciona evidencia directa de la función de las proteínas PCL en el reclutamiento de PRC2 y la regulación transcripcional.