Chemical Basis of Chromatin
Structurally, chromatin is a deoxynucleoprotein—a complex consisting of a single DNA molecule and specific proteins associated with it (along with a small amount of RNA).
Chromatin proteins are divided into two major groups based on their physicochemical properties:
- Histones (basic proteins). These make up the vast majority of chromatin proteins. They are rich in arginine and lysine, amino acids with positively charged side chains. This positive charge allows them to tightly bind to the negatively charged phosphate groups of DNA. The interaction between histones themselves is mediated by hydrophobic residues (e.g., valine).
- Non-histone (acidic) proteins. Despite their lower mass, they are extremely diverse. They include structural proteins (for higher levels of compaction), enzymatic proteins (which temporarily bind to DNA for replication or repair), and regulatory proteins that control enzyme access to specific regions of the genome.
First and Second Levels of Packaging
DNA packaging is a strictly sequential process.
The first level of compaction is called the nucleosomal level. Under an electron microscope, it visually resembles "beads on a string" with a thickness of about 10 nm. The main structural unit here is the nucleosome. Its core consists of a protein octamer: two molecules each of histones H2A, H2B, H3, and H4. The DNA molecule wraps around this globular protein "spool" approximately 1.8 turns. Neighboring nucleosomes are connected by a linker DNA segment, which is associated with histone H1. This level is characteristic of euchromatin; it is present almost constantly and does not hinder transcription (DNA is capable of transiently uncoiling from the globule for fractions of a second). The linear length of the molecule is reduced by 6.2 times.
The nucleomeric (second) level is formed when the H1 histone molecules of neighboring nucleosomes interact with each other. The thread coils into a super-helix (nucleomere), combining 5–8 nucleosomes into a "super-bead." The thickness of this fiber reaches 30 nm. It is important to understand that at this stage, DNA becomes largely inaccessible to enzymes, which is why active euchromatin lacks this level of packing.
Higher Levels of Compaction
Further condensation requires a shift in the stabilization mechanism: non-histone (acidic) proteins take over the primary role instead of histones.
At the chromomeric (third) level, the fiber begins to form multiple loops. These loops group into complex structures called rosettes. The bases of the loops in a rosette are anchored by a common protein center attached to the nuclear matrix. In heterochromatin during interphase, these rosettes are arranged rather loosely, and compaction stops at this stage.
During preparation for cell division (mitosis), packing reaches its maximum, forming metaphase chromosomes:
- Chromonemal level. Loops and rosettes come into close proximity, forming a dense fiber 300 nm thick.
- Chromatid level (fourth). The chromonema is further coiled or folded into loops, forming chromatid segments connected by short linkers (upon damage, the chromosome breaks precisely at these sites). The thickness of the finished chromatid is 700 nm.
The final metaphase chromosome, consisting of two sister chromatids, has a thickness of 1400 nm. At this final stage, the linear length of the original DNA molecule is reduced by 10,000 times.