Protein Composition of Chromatin
All proteins associated with nuclear DNA are divided into two major categories: histone and non-histone proteins.
Histones are low-molecular-weight proteins (11 to 22 kDa). Their amino acid composition is rich in basic amino acids—lysine and arginine. These side chains give the molecules a strong positive charge, which is critical for their function.
Non-histone proteins are a highly diverse fraction. They include:
- Enzymes involved in nucleic acid synthesis (DNA and RNA polymerases, helicases).
- Specific transcription and replication regulatory proteins.
- Additional proteins responsible for higher-order levels of DNA compaction.
Nucleosomal Organization
The fundamental structural unit of chromatin is the nucleosome. It is formed through electrostatic interactions: the positively charged amino acid residues of histones are attracted to the negatively charged phosphate groups of the DNA sugar-phosphate backbone.
The structure of a nucleosome includes the following elements:
- Nucleosome core (core particle): A protein octamer consisting of eight histone molecules (two molecules of each of four different types).
- Core DNA: A segment of double-stranded DNA approximately 146 base pairs long that wraps tightly around the protein core, forming about 1.75 turns.
- Linker DNA: A free stretch of DNA about 30 base pairs long connecting adjacent nucleosomes. A specialized linker histone, H1, is associated with this connecting region.
Heterochromatin and Mechanisms of Repression
Heterochromatin consists of densely packed regions of genetic material. In this state, genes are transcriptionally inactive (stably repressed).
Stable gene inactivity in heterochromatin is maintained by three key factors:
- An initially high level of DNA chain condensation (compaction).
- Nucleosome formation (tight binding of the strand to histones, which physically blocks access to genes).
- Methylation of deoxycytidine at CpG sites. The addition of methyl groups alters the local chromatin conformation, creating an insurmountable barrier for transcription enzymes.
Euchromatin and Differential Gene Activity
Euchromatin consists of decondensed, active (or potentially ready for activation) chromatin regions where the cell's active genes are located. These areas show increased sensitivity to DNases.
Transitioning to an active state requires weakening the ionic bonds within the nucleosome. This is achieved through chemical modifications of histones:
- Acetylation or methylation of amino groups in lysine and arginine side chains.
- Phosphorylation of serine residues.
These reactions reduce the net positive charge of the histone octamer, causing it to hold the negatively charged DNA less tightly.
> Clinical Example: The set of genes is identical in all somatic cells of the body (with the exception of lymphocytes undergoing genetic rearrangements). However, their activity is strictly tissue-specific. For example, the $\beta$-globin gene in erythroid progenitor cells (reticulocytes) is located within euchromatin and actively transcribed, whereas in muscle tissue the exact same gene is hidden in heterochromatin and completely silenced.