BIOL 265 Lecture Notes - Lecture 23: Histone H1, Histone H2B, Histone H2A
15 Apr 2019
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BIOL 265 Genetics
Tuesday April 2nd 2019
Lecture 24
Control of Gene Expression in Eukaryotes
1. Gene Regulation in Behaviors vs Eukaryotes
• Both bacteria and eukaryotes utilize DNA-binding proteins to regulate ability of RNA
pol. to initiate transcription
• Each eukaryotic gene usually has its own promoter (unlike the structural genes of
bacterial operons)
• Chromatin structure regulates transcription in eukaryotes (not the case in bacteria)
• Transcription and translation separated in time and space in eukaryotes… these 2
processes are coupled in bacteria
2. Eukaryotic Chromosomes: Chromatin Structure
• Eukaryotic DNA is organized into chromatin (DNA complexed with protein)
• Histones:
o 5 types of canonical histones: H1, H2A, H2B, H3, H4
o Net positive charge (allows interaction with negative charges of DNA)
• Nucleosome (‘beads on a string”): DNA wound around histone core (octamer of 8
histones; 2 copies of H2A, H2B, H3, H4) at regular intervals
o About 2 turns of DNA wrapped around histone core
o Linker DNA: intervals of DNA between nucleosomes not bound to histones
o Histones have a stretch of 11-37 amino acids at N-terminus of protein (“tails”) that
are mostly positively charged
▪ Also interacts with DNA of neighboring nucleosomes
o Histone H1 binds where DNA enters and leaves nucleosomes (“clamps DNA”)
BIOL 265 Genetics
Tuesday April 2nd 2019
Lecture 24
o Chromatin further organized into higher levels of organization – this further compacts
DNA, ultimately leading to the chromosome structure
3. Changes in Chromatin Structure Affect Gene Expression
• Chromatin organization of DNA needs to be altered in order for transcriptional
machinery to bind DNA and activate transcription
• DNA of regions around transcriptionally active genes are more relaxed
o Can test this out by demonstrating accessibility to enzymes such as DNase I that cuts
phosphodiester bonds in DNA
• DNaseI hypersensitive sites: usually located upstream of start site of transcription of
genes and their increased sensitivity to being cut by DNase I correlates with active
transcription
o Usually sites for binding transcription regulatory proteins
• 3 mechanisms regulate chromatin structure:
o Histone modifications
▪ Histones have 2 domains:
− Domain that associates with other histones and DNA
− Positively charged N-terminal tail that interacts with phosphates of DNA of
the same nucleosome or of a neighboring nucleosome
▪ Histone tails often undergo modifications by histone-modifying enzymes (ex.
histone acetyl transferase, histone deacetylase)
− Phosphorylation/dephosphorylation
− Methylation/demethylation
− Acetylation/deacetylation
BIOL 265 Genetics
Tuesday April 2nd 2019
Lecture 24
▪ There are many other chemical modifications as well
▪ Methylation: either activation or repression of transcription depending on which
particular amino acid in histone tail is modified and the number of methyl groups
attached
▪ Phosphorylation/acetylation: usually enhances transcription by weakening
interaction of histone with DNA (introduces negative charges on amino acid)
▪ Combination of chemical modification of particular amino acids of specific
histones at particular sites along chromatin provide a code (histone code) which
indicates whether a gene is transcriptionally active or not
o Chromatin remodeling complexes
▪ Bind DNA, reposition nucleosomes along DNA, and require ATP for thie
function
▪ Some slide nucleosomes along DNA; others eject nucleosomes, or replace core
histones with histone variants
▪ Target to DNA sequences by:
− Binding transcriptional activators or repressors that binds specific DNA
sequences
− Biding pre-existing histone modifications
