Time for cell division: no gene expression

Time for replication, transcription

Chromosomes contain the genetic material Genes are physically located within the chromosomes Chromosomes are composed of DNA and proteins Primary function of genetic material is to store needed information

Typical chromosome contains a single, linear, double-stranded DNA molecule DNA must be folded and packaged Chromatin is the DNA-protein complex making up chromosomes

Chromatin is the combination of DNA and proteins found in eukaryotic chromosomes. Proteins in chromatin are:
histones: small, positively charged non-histone proteins: transcription factors, enzymes

Packaging of DNA with proteins leads to compacted structure, which facilitates fitting the DNA into the nucleus

Stains darkly (highly condensed) Repetitive sequences Replicates later in the cell cycle Little or no recombination Transcriptionally repressive: silences gene expression

Stains lightly (decondensed) Single copy sequences (genes) Replicates early in the cell cycle Recombines Transcriptionally active: permissive for gene expression

 How do you fit approximately 2 meters (human diploid nucleus) into a space that averages maybe 5 millionths of a meter wide? How do you replicate, repair and transcribe tightly packaged DNA?

Diameter of nucleus = 5-10 mm DNA must be packaged to protect it, but must still be accessible to allow gene expression and cellular responsiveness

1. 2. 3. 4.

Nucleosome (11 nm) Solenoid (30 nm) Loops (300 nm) Coiled loops (700 nm)

5.

Metaphase chromosome (1400 nm)

Level 1: nucleosome formation

Level 2: 30 nm fiber

Level 3: Nuclear scaffolding

Level 4: Mitotic (metaphase) chromosome

Nucleosomes are formed by winding about 200 base pairs of the DNA duplex around a core of histone proteins. The histone core is made of:
2 2 2 2 molecules molecules molecules molecules histone histone histone histone H2A H2B H3 H4

Another histone, H1, binds outside the core.

string on a bead for obvious reasons Linker can vary (8-114bp or more) Compaction ratio is approx 7 fold

30 nm fiber is coil of nucleosomes with 6/turn

A 30 nm diameter chromatin fiber

The zig-zag model, H1 histone has a role in contraction of nucleosomes Compaction ratio approx 100 fold

The 30nm fiber is organized to loops that can be opened up individually

300 nm coiled chromatin fibers radial loops

Form a structural scaffolding to which loops of chromatin are attached nuclear matrix (or chromosome scaffold) 2 scaffold proteins are found (Non histones proteins) 30-nm fibers interact with the nuclear matrix Compacts 30-nm fiber by participating in the formation of radial loop domains Anchored to nuclear matrix

Haploid genom: 2 m

1. Total lenght of mitotic chromosome is:180 mm