Chromosome Structure and Chromatin

Course Information

  • Course: MCB 250

  • Instructor: Dr. James M. Slauch

  • Department: Microbiology

  • Vcast: 20

Chromosome Structure and Chromatin

Overview of Chromosomes

  • Chromosomes are the structures that carry genetic information within cells.

Specified Organisms and Chromosome Content

  • A table showcases DNA, gene, and chromosome content of various species:

    • Escherichia coli (bacterium)

    • Total DNA: 4,600,000 base pairs (bp)

    • Chromosomes: 1

    • Genes: ~4,300

    • Oryza sativa (plant)

    • Total DNA: 180,000,000 bp

    • Chromosomes: 18

    • Genes: ~13,600

    • Drosophila melanogaster (fruit fly)

    • Total DNA: 125,000,000 bp

    • Chromosomes: 10

    • Genes: ~25,500

    • Arabidopsis thaliana (plant)

    • Total DNA: 480,000,000 bp

    • Chromosomes: 24

    • Genes: ~57,000

    • Mus musculus (mouse)

    • Total DNA: 2,500,000,000 bp

    • Chromosomes: 40

    • Genes: ~26,000-29,000

    • Saccharomyces cerevisiae (yeast)

    • Total DNA: 12,068,000 bp

    • Chromosomes: 16+ (haploid variations exist)

    • Genes: ~5,800

    • Caenorhabditis elegans (nematode)

    • Total DNA: 97,000,000 bp

    • Chromosomes: 12*

    • Genes: ~19,000

    • Homo sapiens (human)

    • Total DNA: ~3,200,000,000 bp

    • Chromosomes: 46

    • Genes: ~25,000

  • Notes:

    • *Diploid chromosome number applies to all eukaryotes except yeast.

    • *Haploid chromosome number; wild yeast strains generally have eight or more sets.

    • *For females, with two X chromosomes; males have one X (no Y), totaling 11.

E. coli Chromosome

  • Chromosomal structure in E. coli:

    • The E. coli chromosome is organized in a closed circular structure.

    • Some bacteria possess linear chromosomes.

    • Bacterial DNA is compacted by proteins termed “nucleoid” proteins.

  • Higher-order structure:

    • Nucleoid observed in electron micrographs.

    • Details about scaffolding are uncertain; potential candidates include unknown proteins and enzymes such as gyrase/topology I.

    • This structure is dynamic and non-static.

    • There is no evidence that a specific segment of DNA remains attached to the scaffold; all regions can interconnect freely.

The Compaction Problem in Eukaryotic Cells

  • Eukaryotic chromosomal compaction is significantly more complex than in bacteria:

    • A human cell contains approximately $3 imes 10^9$ base pairs per haploid set.

    • Total linear DNA length:

    • 3imes109extbpimes3.4extA˚/bp=1010extA˚=1extm3 imes 10^9 ext{ bp} imes 3.4 ext{ Å/bp} = 10^{10} ext{ Å} = 1 ext{ m}

    • For diploid cells, approximately 2 meters of DNA fit into a nucleus with a diameter of 10-15 μm.

Chromatin in Eukaryotic Cells

  • Chromatin:

    • The complex of DNA and associated proteins in the nuclei of eukaryotic cells.

    • Major Proteins:

    • Histones are prominent proteins associated with eukaryotic DNA.

    • Many non-histone proteins also contribute to chromatin structure.

    • Approximately half of the mass of a eukaryotic chromosome consists of protein.

Forms of Chromatin (Electron Micrographs)

  • Various forms of chromatin observed:

    • 10-nm fiber: Represents the basic unit of chromatin structure; often depicted as "beads on a string."

    • 30-nm fiber: A more highly compacted form.

    • Differences between chromatin isolated at physiological salt levels versus low salt levels.

Nucleosome Structure

  • The Nucleosome:

    • Fundamental repeating unit of chromatin, referred to as the "bead on a string" model (10 nm fiber).

    • Features:

    • DNA wraps around a histone core approximately 1.67 times.

    • Composed of about 146 base pairs of DNA, plus an additional 20-60 base pairs of linker DNA.

  • Histone Proteins:

    • Histones vary in size (11-21 kDa) and composition (20-25% of amino acids being lysine or arginine).

    • The core consists of four protein types (H2A, H2B, H3, H4), with two copies of each forming a disk-like structure for DNA wrapping.

    • The linker protein H1 interacts with core histones to promote stability and compaction.

Conservation Among Histones

  • Histones are highly conserved across eukaryotic species:

    • Example of histone H4: Only 2 amino acid differences observed between bovine and pea variants, highlighting minimal divergence over $10^9$ years since plant/animal lineages split.

  • Variability exists with histone H2, which has multiple variants in humans, allowing dynamic functions such as gene silencing and DNA repair to occur.

Nucleosome and DNA Interaction

  • Histones bind to the DNA backbone, resulting in DNA bending:

    • Histones share a common structural configuration known as the "histone fold."

    • Interactions primarily occur with phosphate groups and select minor groove bases, not dictated by DNA sequence.

Structural Features of Nucleosomes

  • Histone core components:

    • Includes H3, H4, H2A, and H2B, each having associated amino-terminal tails (NTDs).

    • Approximately 25-30% of total mass of core histones involves NTDs extending from the histone core, contributing to the dynamic nature of chromatin.