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The genome refers to all of the genetic material in an organism. It can range from a few million base pairs in microbial cells to several billion base pairs in many eukaryotic organisms. Genome assembly refers to the process of taking the DNA sequencing data and putting it all back together in a correct order to create a close representation of the original genome. This is followed by the identification of functional elements on the newly assembled genome, a process called genome annotation.
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Human DNA is almost two meters long. However, it is compressed inside a tiny nucleus measuring only a few microns in diameter. To make this degree of compaction possible, DNA is organized into several sequential levels so that it can fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
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Each human somatic cell contains 6 billion base pairs of DNA. Each base pair is 0.34 nm long, meaning each diploid cell contains a staggering 2 meters of DNA. This long DNA strand is packed inside a nucleus measuring only 10-20 microns in diameter with the help of specialized DNA-binding proteins called histones. Together they form a compact DNA-protein complex called chromatin. The chromatin is further compacted into higher-order structures. The highest level of compaction is achieved during...
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Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 meters of DNA. How is such a long DNA strand packed inside a nucleus measuring only 10 - 20 microns in diameter? 
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Eukaryotes have large genomes compared to prokaryotes. To fit their genomes into a cell, eukaryotic DNA is packaged extraordinarily tightly inside the nucleus. To achieve this, DNA is tightly wound around proteins called histones, which are packaged into nucleosomes that are joined by linker DNA and coil into chromatin fibers. Additional fibrous proteins further compact the chromatin, which is recognizable as chromosomes during certain phases of cell division.
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Definición de la arquitectura del genoma en la resolución de pares de bases

Peng Hua1, Mohsin Badat1, Lars L P Hanssen1

  • 1MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

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|June 10, 2021
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Resumen
Este resumen es generado por máquina.

Los investigadores desarrollaron Micro-Capture-C para mapear los contactos de regulación génica en resolución de pares de bases. Este método revela cómo los factores de transcripción y la extrusión del bucle de cromatina mantienen las interacciones potenciador-promotor para la expresión génica específica del tejido.

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Área de la Ciencia:

  • La genómica
  • Biología molecular
  • La epigenética

Sus antecedentes:

  • La expresión génica en los eucariotas está regulada por potenciadores, a menudo distantes de los promotores.
  • El contacto físico entre potenciadores y promotores es crucial para la regulación génica.
  • Los métodos anteriores carecían de la resolución para mapear estos contactos a nivel de proteínas.

Objetivo del estudio:

  • Desarrollar un método de alta resolución para mapear los contactos físicos entre los elementos reguladores de genes.
  • Investigar el papel de los factores de transcripción y la arquitectura de la cromatina en el mantenimiento de las interacciones potenciador-promotor.

Principales métodos:

  • Desarrollado Micro-Capture-C, una técnica de captura de conformación cromosómica.
  • Se ha obtenido una resolución de pares de bases para mapear las interacciones entre los elementos reguladores.
  • Se analizaron los contactos entre potenciadores, promotores y sitios del factor de unión CCCTC (CTCF).

Principales resultados:

  • Se han identificado contactos muy específicos entre potenciadores, promotores y sitios de CTCF.
  • Demostró el papel crítico de los factores de transcripción en el mantenimiento de los contactos potenciador-promotor.
  • Se observó un aumento de las interacciones en el sitio CTCF correlacionadas con promotores y potenciadores activos en la cromatina intervenida.

Conclusiones:

  • Micro-Capture-C proporciona una resolución sin precedentes para el estudio de las interacciones de la cromatina.
  • Los factores de transcripción son jugadores clave en el mantenimiento de bucles potenciador-promotor.
  • La extrusión del bucle de cromatina, dependiente de la carga de cohesión en los elementos reguladores activos, explica la formación de un dominio específico del tejido.