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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.

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Presentation on theme: "Molecular Basis for Relationship between Genotype and Phenotype DNA RNA protein genotype function organism phenotype DNA sequence amino acid sequence transcription."— Presentation transcript:

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

2 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

3 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

4 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.

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

6 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.

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.

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 “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.


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