Medical Genomics Summary Lecture 2 Genome structure

Medical Genomics – Lecture 2 – Genome structure

Structural organization of DNA
The DNA need to be packed to fit in the cell.
During transcription the DNA need to be unfolded, therefore active
genes are less densely packed than inactive genes.
In metaphase the DNA must be folded.

Organization of the nucleus
Heterochromatin; densely packed DNA, transcriptionally inactive
(inert), low gene density (junk DNA such as centromeres, repeats
and MARs)
• Constitutive heterochromatin; regions of DNA that are
always packed in the heterochromatin form
• Facultative heterochromatin; can be hetero- or euchromatic form depending
on transcriptional activity.
Euchromatin; less densely packed DNA, transcriptionally active, high gene density

Spots were transport of molecules take place (nuclear pores, rough
ER) are euchromatin.

Nucleolus/nuclear body; ribosome factory of nucleus for;
• rRNA (ribosomes)
• tRNA
• snRNA molecules

Chromatin condensation states
Condensation of DNA (thicker)
1. The double helix (2 nm)
2. Nucleosomes (11 nm)
3. Chromatin fibers (30 nm)
4. Chromatin coil (300 nm)
5. Chromatin coiled coil (700 nm)
6. Metaphase chromatid (1400 nm)

Histones and nucleosomes
Positively charged histones interact with negatively charged DNA
Nucleosomes is DNA-histone complex.

Histones assemble (verzamelen) into octameric complexes (8 subunits).
2 molecules with H2A, H2B, H3 and H4.

DNA wound 1,65x around the histone octamer.

Chromatin fibers
Histone protein H1 bind to the region of the nucleosome where DNA
enters and exits the nucleosome --> stabilize the nucleosome.

Interaction of H1 molecules with nucleosomes = chromatin