Chromosome: Structure & Organization

Overview

Levels of DNA Packaging

Level 1 - DNA Double Helix (2 nm)

• The fundamental molecule: two antiparallel strands wound in a right-handed helix.
• Each base pair is ~0.34 nm apart; the helix has a diameter of 2 nm.

Level 2 - Nucleosomes ("beads on a string", 11 nm)

• DNA wraps ~1.65 turns (146 nucleotide pairs) around a histone octamer core (2 copies each of H2A, H2B, H3, H4).
• Each nucleosome bead is ~10 nm in diameter.
• Linker DNA (bound by H1 histone) connects adjacent nucleosomes.
• This packing shortens the DNA ~7-fold relative to unfolded DNA.

Level 3 - 30 nm Chromatin Fibril (Solenoid)

• Nucleosomes coil further to form a 30 nm chromatin fibril.
• Six nucleosomes form one turn of this solenoid coil.
• Achieves ~40-fold compaction relative to unfolded DNA.

Level 4 - Loop Domains (~300 nm)

• Long 30 nm fibrils form radial loops (each containing ~15,000-100,000 base pairs) anchored to a central chromosome scaffold of non-histone proteins (topoisomerase II, condensin).

Level 5 - Metaphase Chromosome (~1,400 nm)

• During mitosis, the loop domains condense further into the highly compact metaphase chromosome visible under light microscopy.

Key Structural Components

Histones

• Small, positively charged (basic) proteins rich in lysine and arginine.
• Their positive charge attracts negatively charged DNA phosphate backbone.
• Five main types: H1, H2A, H2B, H3, H4.
• H2A, H2B, H3, H4 form the octamer core; H1 is the linker histone.
• Posttranslational modifications (acetylation, methylation, phosphorylation) regulate chromatin compaction and gene expression.

Non-Histone Proteins

• Scaffold proteins (structural role).
• Transcription factors, RNA polymerases, DNA repair enzymes (functional roles).
• Regulate gene activation and chromosome architecture.

Centromere and Telomere

Centromere

• A specific DNA region where the two sister chromatids are held together after replication.
• Serves as the attachment point for the kinetochore and spindle microtubules during cell division.
• Chromosome types based on centromere position:

Telomeres

• Repetitive DNA sequences (TTAGGG repeats in humans) at the ends of chromosomes.
• Protected by shelterin protein complex.
• Prevent chromosome ends from being recognized as double-strand breaks.
• Shorten with each cell division - a key indicator of cellular aging and replicative lifespan.
• Maintained by the enzyme telomerase (active in stem cells, germ cells, most cancer cells).

Chromatin States: Euchromatin vs. Heterochromatin

• Constitutive heterochromatin: permanently condensed (e.g., centromeric/pericentromeric regions, most of the Y chromosome).
• Facultative heterochromatin: can switch between active/inactive states (e.g., the inactive X chromosome = Barr body).

Chromosome Nomenclature

• The short arm is designated "p" (from French petit).
• The long arm is designated "q".
• Bands are numbered outward from the centromere; e.g., 14q32 = second band, third region of the long arm of chromosome 14.

Human Chromosome Complement

• 46 chromosomes total (diploid = 2n).
• 22 autosomes in pairs (chromosomes 1-22) + XX (female) or XY (male).
• Gene density is unequal: chromosomes 19 and 22 are gene-rich; chromosomes 4 and 18 are relatively gene-poor.
• ~60-70% of the genome is single/low-copy DNA; 30-40% is repetitive (satellite DNA, interspersed sequences like SINEs and LINEs).

• Emery's Elements of Medical Genetics and Genomics - Chromosome Structure section
• Guyton & Hall Textbook of Medical Physiology - Chromosomes and Their Replication, p. 59
• Histology: A Text and Atlas - Chromatin, pp. 234-236
• Basic Medical Biochemistry (6e) - Chromosome Structure and Nomenclature, p. 650