Nucleosome

A nucleosome is the fundamental structural unit of chromatin, found in the nuclei of eukaryotic cells. It consists of DNA wrapped around a core of histone proteins, forming a repeating structure that helps package DNA into a compact and organized form. The nucleosome plays a critical role in both DNA packaging and gene regulation.

Structure of a Nucleosome

1. Histone Core:
   • The nucleosome core is an octamer composed of eight histone proteins:
     • Two copies each of H2A, H2B, H3, and H4.
   • These histones form a protein core around which DNA wraps.
2. DNA:
   • Approximately 147 base pairs of DNA are wrapped around the histone octamer, forming 1.65 superhelical turns.
   • The DNA-histone interaction is stabilized by the positive charge of the histones and the negative charge of the DNA phosphate backbone.
3. Linker DNA:
   • The DNA segment between two nucleosomes, called linker DNA, varies in length but is typically 10–80 base pairs long.
4. Linker Histone (H1):
   • Histone H1 binds to the linker DNA and stabilizes the nucleosome, promoting further chromatin compaction into higher-order structures.

Functions of a Nucleosome

1. DNA Packaging:
   • The nucleosome compacts DNA by approximately sevenfold, enabling long DNA molecules (~2 meters per cell) to fit within the tiny nucleus (~6 micrometers in diameter).
2. Gene Regulation:
   • The position and structure of nucleosomes influence the accessibility of DNA to transcription factors and enzymes:
     • Loosely packed nucleosomes (euchromatin) allow gene expression.
     • Tightly packed nucleosomes (heterochromatin) repress gene expression.
3. Protection of DNA:
   • Nucleosomes protect DNA from damage by shielding it from nucleases and other environmental factors.
4. Facilitation of DNA Processes:
   • Nucleosomes are dynamically reorganized during processes such as:
     • DNA replication.
     • Transcription.
     • DNA repair.

Nucleosome Assembly

1. Histone Chaperones:
   • Specialized proteins called histone chaperones assist in the assembly of histones and DNA into nucleosomes.
2. Dynamic Remodeling:
   • ATP-dependent chromatin remodeling complexes (e.g., SWI/SNF) can reposition, eject, or restructure nucleosomes to regulate DNA accessibility.

Higher-Order Chromatin Structure

1. Beads-on-a-String:
   • Nucleosomes connected by linker DNA resemble “beads on a string” when observed under an electron microscope.
   • This is the most relaxed form of chromatin.
2. 30-nm Fiber:
   • Linker histone H1 promotes further folding of nucleosomes into a 30-nm fiber, creating a more compact structure.
3. Chromosome:
   • During cell division, nucleosomes condense into even higher-order structures to form visible chromosomes.

Nucleosome Dynamics

1. Post-Translational Modifications (PTMs):
   • Histone tails protruding from the nucleosome are subject to chemical modifications, such as:
     • Acetylation: Loosens chromatin, promoting gene expression.
     • Methylation: Can activate or repress genes, depending on the site.
     • Phosphorylation: Plays roles in DNA repair and chromatin condensation.
2. Remodeling Complexes:
   • Enzyme complexes reposition nucleosomes along the DNA to expose or hide specific genes.

Clinical Relevance of Nucleosomes

1. Epigenetics:
   • Nucleosome modifications influence gene expression patterns without altering the DNA sequence.
   • Dysregulation of these modifications is linked to diseases such as cancer and developmental disorders.
2. Autoimmune Disorders:
   • In autoimmune diseases like systemic lupus erythematosus (SLE), nucleosomes released during cell death can act as antigens, triggering an immune response.
3. Therapeutic Targets:
   • Drugs targeting histone-modifying enzymes (e.g., histone deacetylase inhibitors) are being developed to treat cancer and other conditions.

Summary

The nucleosome is the basic structural and functional unit of chromatin, consisting of DNA wrapped around histone proteins. It enables efficient DNA packaging, regulates gene expression, and protects genetic material. The dynamic nature of nucleosomes, influenced by chemical modifications and remodeling, is crucial for cellular processes such as transcription, replication, and DNA repair.