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

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

Eukaryotic Gene Regulation - Transcription Expression of genes can be: - constitutively on (housekeeping genes... ~15,000 in humans) - regulated (temporally or spatially... up to unique proteins in differentiated cell) Differentiation is a manifestation of genes being selectively turned off. Regulation of gene expression involves: - cis-acting regulatory elements - trans-acting transcription factors

Transcription factors have: 1.DNA binding domain (interact with promoter-proximal elements or enhancers/silencers) 2.Transactivation domain (activate or repress transcription, involved in protein/protein interaction) Transcription Factors

Structural Families of Transcription Factors and Regulatory Proteins: Helix-Turn-Helix: Zinc-Finger: Leucine Zipper: Helix-Loop-Helix: Many homeotic genes code for TF's of this class. Many steroid hormone receptor protein TF's belong to this class. Proto-oncogenes such as c-jun and c-fos are genes that encode TF's of this class. Certain proto-oncogenes and genes involved in differentiation encode TF's of this class.

Structural Families of Transcription Factors and Regulatory Proteins: Zinc-Finger: Leucine Zipper: Helix-Loop-Helix:

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  -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  -interferon gene is activated during viral infection.

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.

“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.