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Chromatin Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
Topologically Associated Domains (TADs)
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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...
Co-activators and Co-repressors02:04

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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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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...
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...

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La reubicación de genes dependiente de la metilación de ncRNA y Pc2 entre estructuras nucleares media programas de

Liuqing Yang1, Chunru Lin, Wen Liu

  • 1Howard Hughes Medical Institute, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0648, USA.

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Resumen

La metilación de la proteína Polycomb 2 (Pc2) controla el movimiento de genes de crecimiento entre estructuras nucleares a través de ARN no codificantes (ARNnc). Esto vincula la arquitectura nuclear con la regulación de la expresión génica.

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Área de la Ciencia:

  • Biología Molecular Biología Molecular
  • Biología celular Biología celular.
  • La epigenética es la epigenética.

Sus antecedentes:

  • Los núcleos eucariotas poseen estructuras vinculadas a los ARN no codificantes (ARNnc).
  • El papel de estas estructuras en la regulación de la transcripción no se entiende bien.

Objetivo del estudio:

  • Investigar la relación entre las estructuras arquitectónicas nucleares, los ncRNA y la regulación transcripcional.
  • Para dilucidar el mecanismo por el cual los genes de control de crecimiento se reubican dentro del núcleo.

Principales métodos:

  • Investigó el papel de la proteína Polycomb 2 (Pc2) en la metilación y la desmetilación.
  • Estudió la unión de Pc2 a los ncRNAs TUG1 y MALAT1/NEAT2.2.
  • Se examinó el impacto en la reubicación de genes entre los cuerpos de policombos (PCG) y los gránulos de intercromatina (ICG).
  • Se analizaron los efectos en el conjunto de corepressor / coactivador y lectores de códigos de histona.
  • Se evaluó el papel de la interacción NEAT2-Pc2 en la SUMOilación E2F1 y la activación de genes.

Principales resultados:

  • El estado de metilación de Pc2 dicta la reubicación de los genes de control de crecimiento entre PcG e ICG.
  • Pc2 se une a ncRNAs específicos (TUG1 en PcGs, MALAT1 / NEAT2 en ICGs) en función de su estado de metilación.
  • Los ncRNA facilitan el ensamblaje de complejos proteicos reguladores e influyen en el reconocimiento de la marca de histona.
  • La unión de NEAT2 al Pc2 no metilado promueve la SUMOilación E2F1, activando los genes de crecimiento.

Conclusiones:

  • Una vía molecular conecta los ncRNA específicos de la estructura subnuclear y la metilación de proteínas a la reubicación de genes.
  • Esta vía logra programas coordinados de expresión génica al vincular la arquitectura nuclear con el control de la transcripción.
  • Los hallazgos revelan un nuevo mecanismo para regular los genes de control de crecimiento a través de cambios dinámicos en la organización nuclear.