Medical Biology: Chromatin Structure

Chromatin

• Chromatin is a complex of DNA, histone, and non-histone proteins.
• It can be stained with basic dyes, and the Feulgen reaction is a specific stain for DNA identification.

Euchromatin and Heterochromatin

• Chromatin inside an interphase eukaryotic cell nucleus can be divided into two classes based on its state of condensation:
  • Euchromatin: lightly stained, invisible with light microscopy, but visible with electron microscopy. It is an uncoiled, dispersed form of chromatin, active, and transcriptionally active. DNA surface is available for transcription.
  • Heterochromatin: darkly staining, visible form of chromatin. It is a coiled, condensed, and folded form of chromatin, inactive, and transcriptionally silent.

Heterochromatin

• Examples of cells with heterochromatin include lymphocytes and sperm.
• Heterochromatin localizes to the nuclear periphery and undergoes replication only after euchromatin replication is complete.
• It is highly concentrated in specific chromosomal regions, such as centromeres and telomeres.

Types of Heterochromatin

• Constitutive heterochromatin (α-heterochromatin):
  • DNA is permanently inactive.
  • Transcriptionally silent.
  • Remain condensed at all times.
  • Never transcribed.
  • Do not contain genes.
  • Contain simple repeating DNA sequences (repetitive DNA sequences).
• Facultative heterochromatin (β-heterochromatin):
  • Not permanently maintained in the condensed state.
  • Undergoes periodic dispersal.
  • During these times, transcriptionally active (activable).
  • Contains genes.
  • Example: one of the X chromosomes in female (X chromatin).

The Barr Body

• A heterochromatin mass, 1 μm in diameter.
• Seen in most mammals, including humans.
• Found only in female cells but not in male cells.
• Discovered in 1949 by Barr.
• Well-stained round body attached to the nucleolus in neurons, neutrophyl granulocyt, and buccal epithelium.

X Chromosome Inactivation

• Females have a mechanism that permanently inactivates one of the X chromosomes in all somatic cells.
• Genetic tests show that the genes in the heterochromatic X chromosome are inactive.
• X chromosome contains thousands of genes.
• Females have double copies of X chromosome genes when compared to males.
• But males have equal amounts of proteins encoded by X chromosome genes.

Mechanisms of X Inactivation

• One of the X chromosomes is converted to heterochromatin early in development.
• Inactivation is randomly determined but once made, the decision is permanent.
• In female cells, some cells inactivate Xp, while others inactivate Xm.
• Adult female is like a patchwork.
• Mechanisms include:
  • DNA methylation.
  • Methylated cytosine binding protein (MeCP2).
  • The key element of X inactivation is a non-coding RNA called Xist.
  • XIST: a large RNA that is expressed by the inactive X and covers the inactive X chromosome.

Molecular Modifications in Heterochromatin

• Protein modifications:
  • Deacetylation of lysin and arginin residues in core histones.
  • Methylation of histones.
• DNA modifications:
  • Methylation of cytosine nucleotides.