MCB 317Genetics and Genomics

MCB 317 Topic 10, part 3A Story of Transcription

Why are Acitvators cartooned as two balls held together by a tether?

Co-activators & chromatin remodeling complexes not shown

General FactorsRNAP

Activators

Properties of Activators

ActivatorsMultiple 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

ActivatorsMultiple functions = multiple domains

• DNA binding domain• Activation domain• Dimerization domain (some)• Ligand binding domain (some)

• Helix-turn-helix• Helix-loop-helix• Homeobox• Zinc finger• Leucine zipper

Activators classified based on their DNA binding domain: Transcription factor families

Activators classified based on their DNA binding domain: Transcription factor families

Different Family Members = Different Binding Site

Protein Domains andStructural Motifs

Protein – DNA interaction

General Properties of Proteins that bind DNA

Helix-turn-helix

Homeodomain

Zinc finger type I structure

LeucineZipper

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

ActivatorsMultiple functions = multiple domains

• DNA binding domain• Activation domain• Dimerization domain (some)• Ligand binding domain (some)

Gene family members

Gene Gene

Gene

Ortholog

Paralog

Orthologs = family members in different speciesParalogs = family members in same species

Blast Search

Yeast = 34 Zinc Finger Txn Factors (Activators)

Ab

Protein

ExpressionPattern

Gene

Gene (Organism 2)Paralogs

Mutant Gene

Biochemistry

Genetics

Mutant Organism

1

2

3

4

78

56 9

10

11

Orthologs and Paralogs

9

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