Nucleosome and Histone Octamer

The nucleosome is the fundamental repeating unit of chromatin: a short stretch of DNA wrapped almost twice around a core of eight histone proteins, the histone octamer. This particle both compacts the genome and creates the first layer of regulation over which DNA sequences are accessible. It is the structural starting point for understanding all of chromatin biology.

Definition

A nucleosome is the basic unit of chromatin, consisting of approximately 147 base pairs of DNA wrapped around a histone octamer composed of two copies each of the core histones H2A, H2B, H3, and H4.

Scope

This topic covers the composition and architecture of the nucleosome core particle and the histone octamer that lies at its centre. It addresses the core histones, the path of DNA around the octamer, the role of histone tails, and how this basic unit relates to the accessibility and higher-order packaging of the genome. It is a reference entry on molecular structure and is not clinical guidance.

Core questions

• What proteins make up the histone octamer and how is DNA arranged around it?
• How does wrapping DNA into nucleosomes both compact the genome and restrict access to it?
• How do histone tails extending from the octamer connect structure to regulation?

Key concepts

• Core histones (H2A, H2B, H3, H4)
• Histone octamer
• Nucleosome core particle (~147 bp)
• Histone tails
• Linker DNA and linker histone H1
• DNA wrapping and superhelical turns

Key theories

Repeating nucleosomal unit of chromatin

Kornberg proposed that chromatin is built from a regular repeating unit of histones and DNA; this insight identified the nucleosome as the elementary particle of genome packaging and was later confirmed at atomic resolution.

Mechanisms

An octamer assembles from an H3-H4 tetramer flanked by two H2A-H2B dimers. Roughly 147 base pairs of DNA wrap about 1.65 left-handed superhelical turns around this protein core, with contacts at regular intervals along the DNA minor groove. The crystal structure resolved by Luger and colleagues showed the precise positions of these contacts and the trajectory of the flexible N-terminal histone tails, which protrude from the particle and serve as sites for chemical modification. Linker DNA connects adjacent nucleosomes, and the linker histone H1 binds at the entry and exit points to stabilize higher-order folding. Because DNA bound on the octamer surface is partly occluded, nucleosome formation inherently limits access to regulatory sequences, and destabilizing or repositioning nucleosomes is a primary route to changing gene activity.

Clinical relevance

The nucleosome is the substrate on which chromatin modifications and remodeling act, so its composition and stability are foundational to understanding epigenetic regulation studied in development and disease. Variations such as histone variants and altered nucleosome stability are areas of active research. This entry describes molecular structure and is not a basis for diagnosis or treatment.

History

Before the mid-1970s the organization of DNA with histones was unclear. Kornberg's 1974 proposal of a repeating histone-DNA unit established the nucleosome model. Over the following two decades, biochemical and structural studies refined the picture, culminating in the 1997 high-resolution crystal structure of the nucleosome core particle, which provided an atomic view of how DNA and the histone octamer interact.

Key figures

• Roger Kornberg
• Karolin Luger
• Timothy Richmond
• Steven Henikoff

Seminal works

• kornberg-1974
• luger-1997

Frequently asked questions

How many histones are in a nucleosome core?

Eight: two copies each of the four core histones H2A, H2B, H3, and H4, together forming the histone octamer around which DNA wraps.

How much DNA is wrapped around one nucleosome?

About 147 base pairs of DNA wrap roughly 1.65 turns around the histone octamer in the nucleosome core particle, with additional linker DNA joining one nucleosome to the next.