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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.