L10 - Chromatin Structure and Gene Transcription Flashcards
Genetic alterations to DNA sequences
Permanently affect gene expression.
Epigenetic changes to chromatin structure
Modulate gene expression. Do not alter DNA sequence Are reversible Facilitate stable changes to gene expression which may persist for the life of a cell Can be erased in the germ line
What are nucleosomes?
Nucleosomes can be covalently modified.
N terminal lysine rich tails (8 of them) of core histones project radially from nucleosomal core.
Covalent modifications differ between condensed inactive and open active chromatin.
Types of covalent modification to core histone N-terminal tails
- Acetylation of lysines
- Methylation of lysines and arginine’s
- Methylation/acetylation to termini lysine and serine side chains
Histone acetyltransferases
Modify lysine residues
Histone code writers
Activates gene transcription
Histone methyltransferases
Exhibit site specificities
Histone code writers
Represses gene transcription
Histone deacetylases
Remove modification
Histone code erasers
Represses gene transcription
Histone demethylases
Remove modification
Histone code erasers
Activates gene transcription
Lysine and arginine methylation effects on gene expression?
- H3-K4 active
- H3-K9 inactive
- H3-K27 inactive
- H3-R17 active
Lysine acetylation effects on gene expression
- H2A active
- H2B active
- H3 active
- H4 active
What does acetylation of histones create binding sites for?
Transcription activators that contain a bromodomain
The bromodomain transcription activator is an epigenetic code reader
Mapping of histone acetylation across genes
Histone acetylation is associated with transcriptionally active promoter sequences
What does methylation of histones create binding sites for?
Transcriptional repressors that contain a chromodomain
Transcriptional activators that contain a PHD zinc finger domain
- Depends on the lysine amino acid residue modified
These are both epigenetic code readers
What is the transcriptional regulatory code?
An epigenetic code that lies on top of the genetic code
Governs when and where genetic information is expressed
How do transcription activator proteins work?
- Nucleosome remodelling
- Histone removal
- Histone replacement
- Histone modifications
- Recruitment of code writers and readers