A. Eukaryotic Chromatin Structure
1. While the single circular chromosome of bacteria is coiled and looped in a complex, but orderly manner, eukaryotic chromatin is far more complex.
2. The estimated 35,000 genes in the human genome includes an enormous amount of DNA that does not program the synthesis of RNA or protein.
a. This DNA is elaborately organized.
b. DNA is associated with protein to form chromatin and the chromatin is organized into higher organizational levels.
3. Level of packing has two effects.
a. Level of packing is one way that gene expression is regulated.
1. Densely packed areas are inactivated.
2. Loosely packed areas are being actively transcribed.
b. Level of packing varies at different stages of the cell cycle.
1. During interphase of the cell cycle, chromatin fibers are usually highly uncoiled and DNA can be replicated.
2. During mitosis, the chromatin coils and condenses to form short, thick chromosomes.
4. Eukaryotic chromosomes contain an enormous amount of DNA relative to their condensed length.
a. Each human chromosome averages about 2 x 10 8 nucleotide pairs.
b. If extended, each DNA molecule would be about 6cm long, thousands of times longer than the cell diameter.
c. This chromosome and 45 other human chromosomes fit into the nucleus.
d. This occurs through an elaborate, multilevel system of DNA packing.
5. Nucleosomes
a. Histone proteins are responsible for the first level of DNA packaging.
1. Their positively charged amino acids bind to negatively charged DNA.
2. The five types of histones are very similar from one eukaryote to another and are even present in bacteria.
b. Unfolded chromatin has the appearance of beads on a string, a nucleosome, in which DNA winds around a core of histone proteins.
1. The beaded string seems to remain essentially intact throughout the cell cycle.
a. Histones leave the DNA only transiently during DNA replication.
b. They stay with the DNA during transcription.
1. By changing shape and position, nucleosomes allow RNA-synthesizing polymerases to move along the DNA.
6. Higher levels of DNA packing
a. As chromosomes enter mitosis the beaded string undergoes higher-order packing.
b. With the assistance of histone 1 the beaded string coils to form the 30nm chromatin fiber.
c. This fiber forms looped domains attached to a scaffold of nonhistone proteins.
d. In a mitotic chromosome, the looped domains coil and fold to produce the characteristic metaphase chromosome.
e. Interphase chromatin is generally much less condensed than the chromatin of mitosis.
1. While the 30nm fibers and looped domains remain, the discrete scaffold is not present.
2. The looped domains appear to be attached to the nuclear lamina and perhaps the nuclear matrix.
f. The chromatin of each chromosome occupies a restricted area within the interphase nucleus and do not tangle with other chromosomes.
g. Interphase chromosomes have areas that remain highly condensed, heterochromatin, and less compacted areas, euchromatin.
1. Heterochromatin cannot be transcribed.