DNA Organization: Nucleosomes and Chromatin

What is chromatin?

The DNA–protein complex in eukaryotic chromosomes that allows DNA to fit in the nucleus through compaction by proteins.

Where are eukaryotic chromosomes located?

In the nucleus of eukaryotic cells.

Why must eukaryotic chromosomes be compacted?

To fit the large amount of DNA (≈2 m per cell) inside the small nuclear space.

What are the main types of DNA sequences in eukaryotic chromosomes?

1. Origins of replication (multiple per chromosome) 2. Centromere (1 per chromosome) 3. Telomeres (2 per chromosome).

What are telomeres?

Protective sequences at chromosome ends that prevent degradation and fusion.

What is the centromere’s role?

Attachment site for kinetochore proteins during chromosome segregation in mitosis and meiosis.

Where are genes located on chromosomes?

Between the centromere and telomeres.

How do genes differ between lower and higher eukaryotes?

Lower eukaryotes (e.g., yeast) have small genes with few introns; higher eukaryotes (e.g., mammals) have longer genes with many introns.

What are non-gene sequences composed of?

Repetitive DNA regions such as telomeres, centromeres, and satellite sequences.

What is the basic unit of chromatin structure?

The nucleosome.

Describe a nucleosome.

A segment of DNA (~145–147 bp) wrapped 1.65 turns around an octamer of histone proteins (2 each of H2A, H2B, H3, and H4).

What is the linker DNA?

The stretch of DNA (8–114 bp, usually ≈55 bp) connecting adjacent nucleosomes.

Which histone is the “linker histone”?

H1 — the largest (≈21 kDa), less-conserved histone that binds DNA between nucleosomes to promote higher-order compaction.

What are histones rich in, and why?

Positively charged amino acids (lysine and arginine) that bind the negatively charged DNA backbone via electrostatic attraction.

How many histone–DNA contact points are in one nucleosome core?

≈14 contact points.

What percentage of chromatin mass is protein?

≈ two-thirds; 95% of chromatin protein are histones (H1, H2A, H2B, H3, H4).

How are core histones arranged?

They share a conserved histone fold that allows “handshake” dimerization: H3–H4 dimers form a tetramer scaffold; two H2A–H2B dimers complete the octamer.

What type of interactions stabilize histone–DNA binding?

Electrostatic attractions between basic histone residues and the acidic DNA backbone.

What structural level follows nucleosomes?

The 30 nm fiber — a more compact arrangement of nucleosomes stabilized by histone H1.

What is the approximate compaction ratio from the “beads-on-a-string” form?

About 7-fold compaction compared to naked DNA.

What is the next level of chromatin organization after the 30 nm fiber?

Formation of radial loop domains attached to the nuclear matrix.

What anchors DNA loops to the nuclear matrix?

Matrix-attachment regions (MARs) or scaffold-attachment regions (SARs).

How large are radial loops typically?

20,000 – 100,000 base pairs (bp).

What two main functions does the nuclear matrix serve?

1. Gene regulation (by localizing loops) 2. Chromosome organization (each chromosome occupies a non-overlapping territory).

What is euchromatin?

Less condensed, transcriptionally active chromatin where 30 nm fibers form radial loops.

What is heterochromatin?

Highly condensed, transcriptionally inactive chromatin with further-compacted radial loops.

During interphase, what form does most chromatin take?

Euchromatin.

List the hierarchy of chromatin packaging.

Level 1: Nucleosome formation → Level 2: 30 nm fiber → Level 3: Nuclear scaffolding (radial loops) → Level 4: Mitotic (metaphase) chromosome.

What is the diameter of the DNA double helix, nucleosome, 30 nm fiber, and metaphase chromatid?

2 nm (helix) → 11 nm (nucleosome) → 30 nm (fiber) → 700 nm (chromatid) → 1400 nm (chromosome).

How does histone H1 facilitate chromatin compaction?

It binds linker DNA and promotes folding of nucleosome arrays into the 30 nm fiber.

Why are histones considered highly conserved?

Their amino acid sequences are almost identical across species — especially H4 (with only 2 variants known).