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 (-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