MCB 317
Genetics and Genomics
MCB 317 Topic 10, part 3
A Story of Transcription
Co-activators & chromatin remodeling complexes not shown
Why are Acitvators cartooned as two balls
held together by a tether?
General Factors
RNAP
Activators
Properties of Activators
Activators
Multiple functions = multiple domains
•
•
•
•
DNA binding domain
Activation domain
Dimerization domain (some)
Ligand binding domain (some)
Genes in Yeast vs. Larger Euk
Reporter gene in yeast ->
use to study activators
Deletion Analysis of Coding Region -> Truncated
Proteins
Domains of Activators
Properties of Activators:
Transcription factor families
Gene Families
• It is more common to create variations of a
useful protein structure than it is to create a
new structure
• Families created by gene duplication and
divergence
Gene Families are Generated by Duplication and Divergence
Activators
Multiple functions = multiple domains
•
•
•
•
DNA binding domain
Activation domain
Dimerization domain (some)
Ligand binding domain (some)
Activators classified based on their DNA binding
domain: Transcription factor families
•
•
•
•
•
Helix-turn-helix
Helix-loop-helix
Homeobox
Zinc finger
Leucine zipper
Activators classified based on their DNA binding
domain: Transcription factor families
Protein
Domains
and
Structural
Motifs
Different Family Members = Different Binding Site
General Properties of Proteins that bind DNA
Protein – DNA interaction
Helix-turn-helix
Homeodomain
Zinc finger type I structure
Leucine
Zipper
Activators
(factors) that
dimerize only
bind DNA as
dimers
Homodimers bind inverted repeats
Homodimers, Heterodimers, Family Members and
Recognition Sites
Zinc-finger type II Heterodimers
Helix-loop-helix dimer
Cell Type Specific Patterns of Txn = Combination of Which
Receptors and Txn Factors (Activators) a Cell Produces
Some Key Activators -> Txn of other Activators
Activators
Multiple functions = multiple domains
•
•
•
•
DNA binding domain
Activation domain
Dimerization domain (some)
Ligand binding domain (some)
Gene family members
Gene
Gene
Ortholog
Gene
Paralog
Orthologs = family members in different species
Paralogs = family members in same species
Blast Search
Yeast = 34 Zinc Finger Txn Factors (Activators)
Biochemistry
1
Gene (Organism 2)
Paralogs
Protein
2
6
4
Ab
9
5
Gene
9
Orthologs and
Paralogs
7
3
8
Expression
Pattern
10
Mutant Gene
Mutant Organism
11
Genetics
Many Types of Steroid Hormones
A Variety of Family Members of Steroid-binding Txn
Factors (Activators)
In General Family Members have similar properties:
Monomer v. dimer, mode of activation/inhibition, even types of genes
regulated: homeodomains -> genes invovled in development
Gene Families
• It is more common to create variations of a useful
protein structure than it is to create a new structure
• Families created by gene duplication and divergence