1. Relationship between Genotype and Phenotype
Molecular Basis for
Relationship between Genotype and Phenotype
genotype
DNA
DNA sequence
transcription
RNA
translation
amino acid
sequence
protein
function
phenotype
organism

2. Enhanceosomes and Synergistic Effect on Transcription
Enhanceosome: protein complex of trans-acting factors bound to appropriate DNA sequences.
Proteins interact synergistically to elevate transcription rate.
In b-interferon gene transcription, TFs recruit a coactivator (CBP) which is needed for transcription to occur normally.
Formation of the enhanceosome and activation of RNA polymerase by coactivator are necessary for efficient transcription.
Transcription of b-interferon gene is activated during viral infection.

3. b-interferon enhanceosome:
Surrounded by two nucleosomes, nuc1 and nuc2.
nuc2 covers TATA box and transcription start site.
Co-activator GCN5 acetylates nuc1 and nuc2.
Acetylation leads to recruitment of co-activators, chromatin remodeling complex, and RNA pol II.

7. Tissue-specific Regulation of Transcription
Regulated transcription depends on:
- specific enhancer for gene(s)
- enhancer-specific activator proteins
- correct interaction between enhancer and activator
Tissue-specific regulation requires that the enhancer-specific activator is present only in cells of that tissue type.
ectopic expression: expression in an abnormal location

8. “Master Switch” Gene
Eye formation requires over 2000 genes.
eyeless (ey) mutation causes small rudimentary eyes to form in Drosophila melanogaster.
Small eyes (Sey, Pax-6) in mouse causes similar phenotype.
Aniridia gene in human (lack of normal iris) shows considerable homology to ey gene.

9. Comparison of ey+ and ey Phenotypes
Wild-type eyes
eyeless (ey) eyes
size of ey eyes

10. eyeless (ey) gene codes for a helix-turn-helix transcription protein.
“Master Switch” Gene
Wild-type eyeless (ey) gene can be induced to be expressed ectopically.
eyeless (ey) gene codes for a helix-turn-helix transcription protein.