5.6
The Nucleosome
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 in…
Proteins play a key role in determining the physical structure of a chromosome. The most abundant of these are small, positively charged proteins called histones. This positive charge allows them to tightly associate with the negatively charged DNA.
During certain stages of the cell cycle, DNA is wound tightly around specific types of histones, forming structures called nucleosomes. Nucleosomes are often described as ‘beads’ on a ‘string’ of DNA.
A nucleosome consists of a few key elements. The first of these is an octamer of histone proteins, two molecules each of H2A, H2B, H3, and H4.
Next, a nucleosome also has a 145 -147 bp length of DNA wrapped around the protein octamer nearly two times.
Together, the histone octamer and the DNA wound around it are known as a nucleosome core particle.
Each of the histones in the nucleosome core particle has a small, positively charged tail consisting of 11-27 amino acids.
The tails extend out from the nucleosome core particle and aid in keeping the negatively charged DNA and the histones associated. Furthermore, the histone tails can interact with tails from neighboring core particles, which facilitates DNA packaging.
A fifth type of histone, H1, plays a key role in nucleosome structure, though it is not part of the nucleosome core particle. H1 binds to the DNA where it joins and then leaves the octamer, acting as a clamp and keeping the DNA in place.
Finally, the nucleosome also encompasses the stretch of linker DNA adjacent to the nucleosome core particle. The linker DNA that separates each core particle can vary in length, from about 30 to 40 base pairs, between cell types.
While the terms nucleosome and nucleosome core particle are often used interchangeably, the nucleosome actually refers to the nucleosome core particle and the adjacent linker DNA.
Altogether, nucleosomes are capable of reducing a long DNA molecule into a chromatin thread that is about one-third of its original length.
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Q1: What is a nucleosome and what role does it play in DNA packaging?
A nucleosome is a structure formed when DNA wraps around a histone octamer, consisting of two copies each of H2A, H2B, H3, and H4 proteins. Approximately 145-147 base pairs of DNA wind nearly twice around this protein core. Nucleosomes function as the fundamental unit of DNA compaction, reducing a long DNA molecule to about one-third its original length and enabling the nearly 2-meter-long human genome to fit within the nucleus.
Q2: Why do histones bind so tightly to DNA in nucleosomes?
Histones are small, positively charged proteins that bind tightly to negatively charged DNA through electrostatic interactions. Each histone in the nucleosome core particle has a positively charged tail consisting of 11-27 amino acids that extends outward and aids in maintaining the association between DNA and histones. These tails also interact with neighboring core particles, facilitating DNA packaging and chromatin structure formation.
Q3: What is the difference between a nucleosome and a nucleosome core particle?
The nucleosome core particle consists solely of the histone octamer and the 145-147 base pairs of DNA wrapped around it. A nucleosome, however, encompasses the core particle plus the adjacent linker DNA that separates each core particle. Linker DNA varies in length from about 30 to 40 base pairs between cell types, making the complete nucleosome a larger functional unit than the core particle alone.
Q4: How does the H1 histone contribute to nucleosome structure?
H1 is a fifth type of histone that binds to DNA at the point where it enters and exits the histone octamer, functioning as a clamp to keep DNA in place. Unlike the core histones, H1 is not part of the nucleosome core particle itself. When DNA is isolated under physiological salt conditions, H1 binding helps stabilize the fiber-like 30-nanometer chromatin structure, preventing DNA from slipping away from the nucleosome.
Q5: What are nonhistone proteins and how do they affect nucleosome function?
Nonhistone proteins are a small proportion of proteins that bind to the nucleosome complex and help maintain DNA compaction and organize long chromatin loops. These proteins play regulatory roles in DNA replication and RNA synthesis. While histones are the primary structural components of nucleosomes, nonhistone proteins contribute to the dynamic regulation and higher-order organization of chromatin beyond the basic nucleosome unit.
Q6: How are nucleosomes visualized when DNA is extracted under low salt conditions?
When DNA is extracted from cells under low salt conditions and examined under a microscope, it resembles beads on a string. The bead-like structures represent individual nucleosomes, while the string represents the free linker DNA connecting them. This appearance reflects the fundamental repeating unit structure of chromatin and demonstrates how nucleosomes organize DNA into a more compact form while maintaining accessibility for cellular processes.
Q7: Why are histone proteins highly conserved across different species?
Histone proteins are highly conserved because they perform essential structural functions in DNA packaging that are critical for cell survival. The amino acid sequences of core histone proteins show remarkable similarity across distantly related species; for example, H3 histone between calf thymus and pea plant differs by only four amino acids. This conservation reflects the fundamental importance of nucleosome structure in organizing and protecting DNA across all eukaryotic organisms.