Chromatin

histones

the fundamental units of chromatin structure

five main proteins (H1, H2A, H2B, H3, and H4)

rich in basic amino acids (lysine and arginine)

nucleosome

146 bp of DNA wrapped around the histone octomer: (H2A, H2B, H3, H4) x 2

histone H1 attached to linker DNA, DNA makes about 1.7 left-hand turns

nucleic acid structure flow

1. metaphase chromosome

2. condensed scaffold-associated chromatin

3. interphase: extended scaffold-associated chromatin

4. 30-nm chromatin fiber of packed nucleosomes

5. beads-on-a-string form of chromatin

6. short region of DNA double helix

acetylation

occurs exclusively in the N-terminal domains, at the highly conserved sites indicated in red

general structure of each of the four core histones

involves a helical “histone fold” domain plus an unstructured, highly basic N-terminal domain

histone acetyltransferases (HATs)

involved in the addition of acetyl moieties to lysine residues in the N-terminal regions of each of the core histones (“histone tails”)

some of the TAFs (TBP-associated factors) have this activity

increased acetylation associated with increased gene expression

histone deacetylases (HDACs)

remove acetyl groups from histones

decreased acetylation associated with decreased gene expression

How does acetylation affect levels of gene expression?

may reduce the affinity of histones for DNA by neutralizing the positive charge on lysine residues

reduces interactions between individual nucleosomes that lead to formation of the 30 nm fibers

DNase I hypersensitive sites

regions of the genome particularly susceptible to experimental digestion by nucleases

associated with actively transcribed regions

stems from the removal or “remodeling” of nucleosomes in these discrete regions, which allows the transcription apparatus to access the DNA

specific example of DNase I hypersensitive sites

position of them in the beta-globin gene cluster are different at different stages of development