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Eukaryotic Gene
Control
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Gene Organization:
•Chromatin: •Complex of DNA and
Proteins•Structure base on DNA
packing
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DNA Packing:
• Histones: positively charged amino acids• Five types (H1, H2A, H2B,
H3,H4)
• DNA- negatively charged phosphate groups
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DNA Packing:
• Nucleosomes: “beads on a string”• Basic unit• DNA wound around two molecules
composed of histones (H2 – H4)• H1 = histone tail
• 10nm
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Higher Level of DNA Packing:
• Coiling of 10nm = 30nm chromatin fiber
• Looped domain = 30nm chromatin fiber attaches to chromosome scaffold = 300nm fiber
• Metaphase chromosome- maximal compaction • 1400 nm
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Heterochromatin:
•Highly condensed interphase DNA•Can not be transcribed
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Euchromatin:
•Less compacted interphase DNA•Can be transcribed
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Differential gene expression on many
levels: • 1. Pre Transcription
• Chromatin
• 2. Transcription
• 2. Post Transcription• RNA processing, transport to cytoplasm,
degradation of mRNA
• 3. Translation
• 4. Post Translation• Cleavage and chemical modification,
degradation of protein
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Examples: Pre-transcription
• Histone Acetylation of chromatin:• Histones = group of 5 proteins associated with
the coiling of DNA (positively charged regions)
• Histone acetylation: acetyl group (-COCH3
• Attached to positively charged regions• Neutralizes the histones• Causes DNA to become loser• Transcription proteins can access the DNA with
greater ease
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• Deacetylation (removing of acetyl groups) creates a tighter, super coiled DNA structure
• Difficult for transcription to proceed
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DNA methylation and demethylation:
• Inactive Mammalian X chromosomes (Barr bodies):• Highly methylated (-CH3) bases,
particularly cytosine• Removing of methyl groups can
activate these genes
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Gene regulation gone wrong:
• Proto- oncogenes:• Normal cellular genes• Code for proteins that stimulate normal
cell growth and division
• Oncogenes:• Cancer causing genes
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How do proto-oncogenes become
oncogenes?• Movement of DNA-
translocation
• Amplification:
• Point mutations:
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Tumor- Suppressor genes
• Genes that inhibit cell division
• Mutation of these genes may stimulate uncontrollable cell growth
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Normal Cell Signaling Interference:
• Interference with a cell signal pathway• 1. can stimulate pathways of the cell
cycle to promote uncontrollable cell division
• 2. can inhibit cell cycle pathways that prevent suppression of cell division allowing uncontrolled cell division