DNA Packaging

Nucleosomes Assembly Nucleosomes are assembled in an ordered fashion! Step 1: Two H3-H4 dimers form a tetramer Step 2: H32:H42 tetramer binds to double stranded DNA Step 3: Two H2A- H2B dimers bind are recruited to the DNA molecule forming a complete nucleosome Step 1 Step 2 Step 3

Eukaryotic Chromosomal Organization Nucleosomes and DNA Compaction DNA wrapping around the histones (10nm) results in 6 fold compaction Needs to be about 10,000 fold—depending on genome size Nucleosomes link together to build a 30-nm fiber with help of Histone H1 https://www.youtube.com/watch?v=9kQpYdCnU14

True nature of the chromosome scaffold remains a mystery. Further compaction Histones alone are not the answer. The histone compaction (with Histone H1) results in about a 40 fold reduction. What does the rest? True nature of the chromosome scaffold remains a mystery.

Histone Modifications How are histone tails modified? P=Phosphorylation Me: Methylation Ac=Acetylation Ub: Ubiquitinylation

Histone Modifications What do these modifications do? Weaken the association of the nucleosome with DNA Inhibit the higher order nucleosome assembly Recruit specific proteins to the chromatin Some proteins can recognize the modified histone tails

Histone Modifications Acetyl groups carries a negative charge. Acetylation of lysine cancels the positive charge Histone tails are more weakly associated with the nucleosomes– thus cannot form higher order assemblies (ie. 30 nm fiber) Tends to decreases packing Methyl groups are neutral. Histone tails maintain association with the nucleosomes. Tends to increase packing