Describe the structure of nucleosome and its role in DNA packaging.

Structure of the Nucleosome

A nucleosome is the fundamental repeating unit of chromatin, resembling a "bead on a string" when observed under an electron microscope. Its structure is precisely organized to facilitate efficient DNA compaction. The nucleosome consists of two primary components:

• Histone Octamer: This is the protein core around which DNA is wrapped. It comprises eight histone proteins, with two copies each of four core histones: H2A, H2B, H3, and H4. Histones are small, highly basic proteins rich in positively charged amino acids like lysine and arginine. This positive charge is crucial for their interaction with the negatively charged phosphate backbone of DNA. The core histones possess a characteristic structural motif called the "histone fold," consisting of three alpha-helices separated by two loops, which facilitates their interaction and assembly into the octamer.
• DNA Segment: Approximately 146-147 base pairs of DNA are wrapped around the histone octamer in about 1.67 left-handed superhelical turns. This tightly wound segment is known as the nucleosome core DNA.
• Linker DNA: Stretches of DNA, varying in length from 10 to 80 base pairs, connect adjacent nucleosome core particles. These are known as linker DNA.
• Linker Histone (H1): While not part of the core octamer, the histone H1 binds to the linker DNA at the entry and exit points of the DNA from the nucleosome. It helps to stabilize the nucleosome structure and is crucial for higher-order chromatin compaction.

The entire nucleosome core particle forms a squat disc-like structure, approximately 11 nm in diameter and 5.5 nm in height.

Role of Nucleosome in DNA Packaging

The nucleosome represents the first and most fundamental level of DNA packaging in eukaryotic cells, enabling the vast length of DNA to fit within the confines of the nucleus. The packaging process involves several hierarchical levels:

1. First Level: Nucleosome Formation ("Beads-on-a-String")

• DNA wraps around histone octamers, forming nucleosomes. This initial level of compaction reduces the DNA length by approximately 5-7 fold.
• When viewed under a low-salt condition, chromatin appears as a "beads-on-a-string" structure, where the "beads" are the nucleosomes and the "string" is the linker DNA.
• This packaging not only compacts DNA but also helps neutralize its negative charge, preventing tangling and protecting it from damage.

2. Second Level: 30 nm Chromatin Fiber (Solenoid or Zigzag Model)

• Nucleosomes, along with the linker histone H1, further coil and fold to form a more compact structure known as the 30 nm chromatin fiber. This further compacts the DNA, shortening its length by another factor of 6, leading to an overall compaction ratio of about 40-50 fold.
• There are two main models proposed for the 30 nm fiber:
  • Solenoid Model: Nucleosomes are tightly wound into a regular, helical structure, with approximately six nucleosomes per turn.
  • Zigzag Model: Nucleosomes are arranged in a less regular, zigzag pattern, with less face-to-face contact between adjacent nucleosomes. The formation of either model can depend on the length of the linker DNA.

3. Third Level and Beyond: Looped Domains, Chromosomes

• The 30 nm fiber undergoes further compaction by forming large loops, often referred to as "loop domains," which are anchored to a non-histone protein scaffold within the nucleus.
• During cell division (mitosis and meiosis), these looped domains condense even further to form the highly compact and visible structures known as chromosomes. This represents the highest level of DNA packaging, with an overall compaction of DNA by up to 10,000-fold.

Beyond mere physical compaction, nucleosomes play a critical role in regulating gene expression. The degree of DNA wrapping around histones influences the accessibility of DNA to transcription factors and other regulatory proteins. Tightly packed chromatin (heterochromatin) is generally transcriptionally inactive, while loosely packed chromatin (euchromatin) is associated with active gene transcription. Chemical modifications to histone tails (e.g., acetylation, methylation) can alter histone-DNA interactions, thereby modulating chromatin structure and gene activity.