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Eukaryotic Gene Control. Gene Organization: . Chromatin: Complex of DNA and Proteins Structure base on DNA packing. DNA Packing:. Histones: positively charged amino acids Five types (H1, H2A, H2B, H3,H4) DNA- negatively charged phosphate groups. DNA Packing: .
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Gene Organization: • Chromatin: • Complex of DNA and Proteins • Structure base on DNA packing
DNA Packing: • Histones: positively charged amino acids • Five types (H1, H2A, H2B, H3,H4) • DNA- negatively charged phosphate groups
DNA Packing: • Nucleosomes: “beads on a string” • Basic unit • DNA wound around two molecules composed of histones (H2 – H4) • H1 = histone tail • 10nm
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
Heterochromatin: • Highly condensed interphase DNA • Can not be transcribed
Euchromatin: • Less compacted interphase DNA • Can be transcribed
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
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
Deacetylation (removing of acetyl groups) creates a tighter, super coiled DNA structure • Difficult for transcription to proceed
DNA methylation and demethylation: • Inactive Mammalian X chromosomes (Barr bodies): • Highly methylated (-CH3) bases, particularly cytosine • Removing of methyl groups can activate these genes
Gene regulation gone wrong: • Proto- oncogenes: • Normal cellular genes • Code for proteins that stimulate normal cell growth and division • Oncogenes: • Cancer causing genes
How do proto-oncogenes become oncogenes? • Movement of DNA- translocation • Amplification: • Point mutations:
Tumor- Suppressor genes • Genes that inhibit cell division • Mutation of these genes may stimulate uncontrollable cell growth
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