Levels of chromosome organization (Compaction of DNA)
A typical eukaryotic chromosome contains 1 to 20 cm (104 to 2 x 10 5 μm) of DNA. During metaphase of meiosis and mitosis, this DNA is packaged in a chromosome with a length of only 1 to 10 micrometer. How is this entire DNA condensed into the compact chromosomes that are present during mitosis and meiosis?
This lecture will explain you the multilevel system of DNA packing which enables DNA to fit into the cell nucleus whose diameter is thousand times lesser than that of the length of DNA.
Eukaryotic DNA is packaged into a set of chromosomes
- In eukaryotes the DNA in the nucleus is divided between a set of different chromosomes.
- For example, the human genome is approximately 3.2 × 109 nucleotides which are distributed over 24 different chromosomes.
- Each chromosome consists of a single, enormously long linear DNA molecule associated with proteins that fold and pack the fine DNA thread into a more compact structure.
- The complex of DNA and protein is called chromatin (from the Greek word chroma, “color,” because of its staining properties).
Eukaryotic DNA Compaction (Levels of chromosome organization)
- The simplest level is the double helical structure of DNA
- At a more complex level, the DNA molecule is associated with proteins and is highly folded to produce a chromosome.
- The winding of DNA around the nucleosome core contributes to DNA’s packing by decreasing its linear extent.
The length of DNA in the nucleus is far greater than the size of the compartment in which it is contained. To fit into this compartment the DNA has to be condensed in some manner. The degree to which DNA is condensed is expressed as its packing ratio.
To achieve the overall packing ratio, DNA is not packaged directly into final structure of chromatin. Instead, it contains several hierarchies of organization.
At least five levels of condensation are required to package the 103 to 105 μm of DNA in a eukaryotic chromosome into a metaphase structure (a few microns long)
1) Nucleosome (primary chromatin structure)
- The first level of packing is achieved by the winding of DNA around a protein core to produce a “bead-like” structure called a nucleosome. This gives a packing ratio of about 6.
- This structure is invariant in both the euchromatin and heterochromatin of all chromosomes.
Refer the following link for more information
2) 30nm fiber or filament (secondary chromatin structure)
This structure gives a packaging ratio of ~40
3) Radial Loops (300nm fiber): The Third Level of Chromatin Organization
- During cellular interphase — the period in which the cell is not actively dividing — “scaffold” proteins fold the 30-nm fibers into a somewhat more compact structure to fit within the nucleus.
- Folding of the 30-nm fiber form looped domains that attached to a scaffold of non-histone proteins
- Numerous loops of DNA (30 -90 loops) attached to a protein scaffold. Each loop is a 30nm fiber with 180 -300 nucleosomes.
- Only certain regions of DNA associate with a nuclear scaffold. The scaffold unattached regions of DNA form loops that radiate out in a spiral fashion. Each loop contains 60 -100kbp of DNA tethered by non histone scaffold proteins
- The DNA in a loop may contain a set of genes with related functions.
Example: In Drosophila complete sets of histone-coding genes seem to cluster together in loops that are bounded by scaffold attachment sites.
Chromosome scaffold: It is the chromosome structure consisting entirely of non histone proteins (Structure that remains when of all the DNA and histone proteins have been removed from a chromosome).
The scaffold itself appears to contain several proteins, notably large amounts of histone H1 (located in the interior of the fiber) and topoisomerase II.
In interphase nuclei, a nuclear matrix is found as a filamentous structure on the interior of nuclear membrane. Chromatin remains attached to this matrix through matrix attachment regions (MARs).
It is believed that the same sequences of DNA work as MAR in interphase nuclei and as SAR (scaffold attachment regions) in metaphase chromosomes. Both matrix and scaffold are proteinaceous in nature
4) Chromatid (700nm diameter)
- The looped domains (300nm chromatin fiber) coil further during mitosis to form a 700-nm chromatid (one of the longitudinal subunits of the metaphase chromosome). Such tight packing makes the genes on the DNA inactive.
- This structure gives a packaging ratio of ~700
5) Metaphase chromosome (1400nm diameter)
- A pair of sister chromatids comprising a chromosome measures about 1400 nm.
- Fully condensed chromosome is 10,000 fold shorter and 400 – fold thicker than DNA alone.
- Metaphase chromosomes are the most condensed of normal eukaryotic chromosomes.
- This structure gives a packaging ratio of ~10,000
- The role of these highly condensed chromosomes is to organize and package the giant DNA molecules of eukaryotic chromosomes into structures that will facilitate their segregation to daughter nuclei without the DNA molecules of different chromosomes becoming entangled and, as a result, being broken during the anaphase separation of the daughter chromosomes.
Intermediate stages during the folding of 300nm fiber into metaphase chromosome
Rosette: 6 loops o DNA together forms one rosette
Coil: 30 rosettes together forms 1 coil
Chromatid (two): One chromatid contains 10 coils