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The Nucleosome02:33

The Nucleosome

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DNA in a human cell is almost 2m long and it is packed inside a tiny nucleus that is only a few microns in diameter. The level of compaction of DNA inside the nucleus is astonishing. It is organized into several sequentially higher levels of compaction to 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.
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...
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The Nucleosome Core Particle01:12

The Nucleosome Core Particle

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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.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
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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.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
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Histone Variants at the Centromere02:30

Histone Variants at the Centromere

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Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
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Histone Modification02:32

Histone Modification

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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.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.7K
Heterochromatin02:38

Heterochromatin

14.2K
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.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
14.2K

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Video Experimental Relacionado

Updated: Aug 26, 2025

Author Spotlight: Efficient Nucleosome Reconstitution for Single-Molecule Techniques
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Author Spotlight: Efficient Nucleosome Reconstitution for Single-Molecule Techniques

Published on: September 6, 2024

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Estructuras del complejo PIC-Mediador ligado al nucleosoma +1

Xizi Chen1, Xinxin Wang1, Weida Liu1

  • 1Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Department of Biochemistry and Biophysics, School of Life Sciences, Shanghai Key Laboratory of Radiation Oncology, and Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College of Fudan University, Shanghai 200032, China.

Science (New York, N.Y.)
|October 6, 2022
PubMed
Resumen

El nucleosoma +1 organiza el complejo de preiniciación (PIC) y el mediador en los promotores eucariotas, facilitando el inicio de la transcripción. Este nucleosoma actúa como una barrera, pero sus patrones de unión específicos son clave para coordinar el ensamblaje PIC-Mediator.

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Área de la Ciencia:

  • Biología molecular
  • La epigenética
  • Regulación genética

Sus antecedentes:

  • La iniciación de la transcripción eucariota implica el ensamblaje del complejo de preiniciación (PIC) en los promotores centrales.
  • El nucleosoma +1, ubicado aguas abajo del sitio de inicio de la transcripción (TSS), se reconoce como una barrera de transcripción.
  • Comprender la interacción entre los nucleosomas y la maquinaria de transcripción es crucial para descifrar la regulación génica.

Objetivo del estudio:

  • Para aclarar el mecanismo molecular de la organización PIC-Mediador en la cromatina.
  • Investigar el papel estructural del nucleosoma +1 en la coordinación del ensamblaje PIC-Mediator.
  • Para revelar cómo el nucleosoma +1 influye en el inicio de la transcripción.

Principales métodos:

  • Análisis estructural de alta resolución del mediador PIC unido al nucleosoma +1.
  • Ensayos bioquímicos para determinar las preferencias de unión y las interacciones.
  • Immunoprecipitación de la cromatina para el estudio de la organización in vivo.

Principales resultados:

  • PIC-Mediator se une preferentemente al nucleosoma T40N, ubicado 40 pares de bases aguas abajo del TSS.
  • Se observaron contactos específicos con los nucleosomas T50N pero no con los T70N.
  • El nucleosoma +1 facilita la organización del PIC-Mediador mediante la unión de la subunidad TFIIH p52 y las subunidades Mediador MED19 y MED26.

Conclusiones:

  • El nucleosoma +1 juega un papel importante en la regulación de la iniciación de la transcripción.
  • Los múltiples patrones de unión de nucleosomas de PIC-Mediator destacan su papel estructural en la coordinación del ensamblaje.
  • Este estudio revela los intrincados mecanismos moleculares que rigen la organización del PIC-Mediador en la cromatina.