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Nucleosome Remodeling02:54

Nucleosome Remodeling

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Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
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Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
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Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
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The Nucleosome01:19

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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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The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
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The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
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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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  2. El Complejo Hexasoma-ino80 Revela La Base Estructural De La Remodelación No Canónica Del Nucleosoma
  1. Home
  2. El Complejo Hexasoma-ino80 Revela La Base Estructural De La Remodelación No Canónica Del Nucleosoma

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El complejo hexasoma-INO80 revela la base estructural de la remodelación no canónica del nucleosoma

Min Zhang1, Anna Jungblut1,2, Franziska Kunert3

  • 1Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.

Science (New York, N.Y.)
|June 29, 2023

Ver abstracta en PubMed

Resumen
Este resumen es generado por máquina.

El complejo INO80 utiliza ATP para remodelar los hexasomas, que carecen de histonas H2A-H2B. Detecta las histonas H3-H4 expuestas para activar la remodelación, revelando nuevos mecanismos de regulación de la cromatina.

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Área de la Ciencia:

  • Biología molecular
  • Biología de la cromatina
  • Biología estructural

Sus antecedentes:

  • La pérdida de los dímeros de histona H2A-H2B ocurre en los genes transcritos activamente.
  • La función de la maquinaria celular con partículas nucleosómicas no canónicas no se entiende bien.

Objetivo del estudio:

  • Elucidar el mecanismo estructural de la remodelación de la cromatina dependiente del ATP de los hexasomas por el complejo INO80.
  • Comprender cómo el INO80 reconoce los hexasomas y cómo se regula esta interacción.

Principales métodos:

  • Análisis estructural del complejo INO80 unido a los hexasomas.
  • Ensayos bioquímicos para estudiar la actividad y la activación del INO80.

Principales resultados:

  • INO80 reconoce el ADN no canónico y las características histónicas de los hexasomas empobrecidos con H2A-H2B.
  • Un reordenamiento estructural cambia el INO80 a un modo de remodelación distinto.
  • La activación de INO80 está directamente mediada por la detección de una interfaz de histona H3-H4 expuesta, independiente del parche ácido H2A-H2B.

Conclusiones:

  • La pérdida de histonas H2A-H2B expone características únicas que INO80 utiliza para la remodelación.
  • La activación de INO80 por histonas H3-H4 expuestas revela una nueva capa de regulación de la cromatina impulsada por la energía.