Chromatin compaction

Chemical basis of chromatin

Structurally, chromatin is a deoxynucleoprotein—a complex consisting of a single DNA molecule and specific proteins bound to it (along with a small amount of RNA).

Chromatin proteins are divided into two large groups based on their physicochemical properties:

• Histones (basic proteins). They constitute the vast majority of chromatin proteins. They are rich in arginine and lysine, which are amino acids with positively charged radicals. It is this "plus" charge that allows them to bind tightly to the negatively charged phosphate groups of DNA. The interaction between the histones themselves is mediated by hydrophobic radicals (e.g., valine).
• Non-histone (acidic) proteins. Despite their lower mass, they are extremely diverse. They include structural proteins (for higher compaction levels), enzymatic proteins (temporarily binding to DNA for replication or repair), and regulatory proteins that control enzyme access to specific genome regions.

First and second levels of packing

DNA packing is a strictly sequential process.

The first level of compaction is called the nucleosomal level. Visually under an electron microscope, it resembles "beads on a string" with a thickness of about 10 nm. The main structural unit here is the nucleosome. Its core is a protein octamer: two molecules each of histones H2A, H2B, H3, and H4. The DNA molecule makes about two turns around this globular protein "barrel." Neighboring nucleosomes are connected by a linker DNA segment, which is associated with histone H1. This level is characteristic of euchromatin, is present almost constantly, and does not interfere with transcription (DNA is capable of freeing itself 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 histone H1 molecules of neighboring nucleosomes begin to interact with each other. The thread twists into a superhelix (nucleomere), combining 5–8 nucleosomes into a "super-bead." The thickness of such a fibril reaches 30 nm. It is important to understand that at this stage DNA is already inaccessible to enzymes, which is why active euchromatin lacks this level.

Higher compaction levels

Further condensation requires a change in the stabilization mechanism: instead of histones, non-histone (acidic) proteins take on the primary role.

At the chromomeric (third) level, the thread 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 interphase heterochromatin, the rosettes are arranged rather loosely, and its compaction stops here.

During the cell's preparation for division (mitosis), packing reaches its maximum, forming metaphase chromosomes:

1. Chromonemal level. Loops and rosettes converge as much as possible, forming a dense thread 300 nm thick.
2. Chromatid level (fourth). The chromonema spirals or folds 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 1,400 nm. At this final stage, the linear length of the original DNA molecule is reduced by 10,000 times.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• The role of regulatory non-histone proteins in gene expression
• Mechanisms of short-term release of DNA from histones during transcription
• Dynamic binding of enzymatic proteins to DNA
• Segmental organization of chromatids and its clinical significance

Other topics in the section "Cell nucleus. Cell division"

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