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: 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 (-COCH 3 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 (-CH 3 ) 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