Transcript No Slide Title

Molecular Basis for
Relationship between Genotype and Phenotype
genotype
DNA
DNA sequence
transcription
RNA
translation
protein
function
phenotype
organism
amino acid
sequence
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.
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.
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
“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.
Comparison of ey+ and ey Phenotypes
Wild-type eyes
eyeless (ey) eyes
size of ey eyes
“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.