5.9
Chromatin Packaging
Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering…
Every human diploid cell contains about 2 meters of DNA compressed inside a tiny nucleus of just a few microns in diameter. The arrangement and coiling of DNA inside the nucleus is therefore highly organized, and tightly regulated.
First, the chromosomal DNA is associated with histone proteins to form a structure called the chromatin. The basic structural and functional unit of chromatin is called a nucleosome. The association of the DNA into nucleosomes shortens the DNA length sevenfold.
Next, a non-core histone protein called H1 binds to each nucleosome. The H1 histone changes the DNA path as it exits the nucleosome, helping to further compact the complex.
These nucleosomes are then stacked on top of each other, generating a shorter and thicker fiber with a diameter of 30 nm, known as 30-nm fibers.
The arrangement of nucleosomes into the 30-nm fiber is explained by a widely accepted Solenoid model. The model proposes that nucleosomes are arranged in a left-handed helical conformation with six or more nucleosomes per turn. This shortens the DNA length by a further 50-fold.
Any chromatin region that is not being actively transcribed or replicated exists in the 30-nm fiber form. On the other hand, the chromatin regions that are actively being accessed exist in an extended beads-on-a-string form.
The 30 nm fibers are coiled further to form loops of around 300 nm length. These fibers are then compressed into 250 nm wide coils.
Later during the metaphase of the cell cycle, the chromatin fibers form highly condensed structures called chromosomes.
The overall compaction ratio of DNA into the chromosome is approximately 1:10000. Once the cell divides, the chromosomes uncoil again.
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Q1: How does DNA fit inside the nucleus of a cell?
Each human diploid cell contains approximately 2 meters of DNA that must fit inside a nucleus measuring only a few microns in diameter. DNA achieves this through hierarchical packaging: it first associates with histone proteins to form chromatin, then organizes into nucleosomes, which compact the DNA sevenfold. These nucleosomes further coil into 30-nm fibers and eventually condense into chromosomes, achieving an overall compaction ratio of approximately 1:10,000.
Q2: What is a nucleosome and what role does it play in DNA packaging?
A nucleosome is the basic structural and functional unit of chromatin, consisting of 147 base pairs of DNA wrapped around eight histone proteins. Under electron microscopy, nucleosomes appear as beads on a string along the chromatin fiber. The association of DNA into nucleosomes shortens DNA length sevenfold, representing the first major level of DNA compaction in the cell.
Q3: What is the solenoid model and how does it explain chromatin structure?
The solenoid model proposes that nucleosomes are arranged in a left-handed helical conformation with six or more nucleosomes per turn. This arrangement generates 30-nm fibers, named for their diameter of approximately 30 nanometers. The model explains how nucleosomes stack and coil to achieve further DNA compaction of approximately 50-fold, with the non-core histone H1 playing an essential role in stabilizing this structure.
Q4: How does chromatin structure change during the cell cycle?
Chromatin exists in different conformational states depending on cellular activity. Regions actively being transcribed or replicated exist in an extended beads-on-a-string form. During metaphase of the cell cycle, chromatin fibers coil further into loops of around 300 nanometers, then compress into 250-nanometer-wide coils, forming highly condensed structures called chromosomes. Once the cell divides, chromosomes uncoil again.
Q5: What is the function of histone H1 in chromatin packaging?
Histone H1 is a non-core histone protein that binds to each nucleosome after DNA wraps around the histone octamer. H1 changes the DNA path as it exits the nucleosome, helping to further compact the complex. In the absence of H1, chromatin fiber turns into irregular clumps of nucleosomes, demonstrating its essential role in organizing nucleosomes into higher-order 30-nm fiber structures.
Q6: What is the overall compaction ratio achieved when DNA is packaged into chromosomes?
The overall compaction ratio of DNA into the chromosome is approximately 1:10,000. This remarkable compression is achieved through multiple hierarchical levels: nucleosome formation reduces DNA length sevenfold, 30-nm fiber formation reduces it another 50-fold, and further coiling into loops and condensed structures during metaphase completes the packaging process.
Q7: How does chromatin packaging relate to gene activity in cells?
Chromatin packaging directly influences gene accessibility and expression. Chromatin regions that are actively being transcribed or replicated exist in an extended beads-on-a-string form, allowing access to transcription machinery. Conversely, any chromatin region not being actively accessed exists in the more compact 30-nm fiber form, making DNA less accessible. This dynamic regulation of chromatin structure controls which genes are expressed at any given time.