1. REGULATION OF GENE EXPRESSION
Chapter 18

2. Gene expression A gene that is expressed is “turned on”.
It is actively making a product (protein or RNA).
Gene expression is often regulated at transcription.
Newly discovered roles of RNA in gene expression

3. Regulation of a metabolic pathway

4. Prokaryotic Gene Regulation
Adjust activity of enzymes already present
Often through negative feedback
Adjust production level of certain enzymes

5. OPERONS Regulation in prokaryotes
Operator – switch segment of DNA in promoter
Operon – the promoter, the operator, and the genes they control
Regulatory gene – long distance from gene that is regulated

6. The trp operon: regulated synthesis of repressible enzymes
trp animation trp tutorial

7. The trp operon: regulated synthesis of repressible enzymes

8. The lac operon: regulated synthesis of inducible enzymes
lac operon animation lac operon tutorial

9. The lac operon: regulated synthesis of inducible enzymes

10. Regulatory gene makes protein (repressor) that inhibits operator
Regulatory protein has inactive and active shape
Corepressor – makes repressor active
Inducer – inactivates repressor

11. Repressible enzymes usually used when cell makes something (ex
Repressible enzymes usually used when cell makes something (ex. tryptophan)
Inducible enzymes usually used when cell breaks something down (ex. lactose)

12. Eukaryotic Gene Regulation
Expression can be regulated at any stage
Differential gene expression – different cells in an organism express different genes from the genome
Not all genes are turned on all of the time!

13. Opportunities for the control of gene expression in eukaryotic cells

14. GENOME ORGANIZATION
1.5% of DNA in humans codes for protein
24% introns and regulatory
Most is repetitive DNA (59%)
Unique noncoding is 15%

15. CHROMATIN
Composed of DNA and proteins called histones
Nucloesome – DNA wrapped around a histone

16. Levels of chromatin packing

17. Eukaryotic Regulation
At DNA level
Chromatin modification, DNA unpacking with histone acetylation (turned on) and DNA demethylation (turned off)
At RNA level
Transcription, RNA processing, transport to cytoplasm
At protein level
Translation, protein processing, transport to cellular destination, protein degradation

18. Regulation of transcription
Transcription factors – mediate the binding of RNA polymerase to the promoter and other regulatory proteins
Enhancers – far upstream of gene; bind to transcription factors; called distal control element

19. Figure 19.8 A eukaryotic gene and its transcript

20. Not many different control elements so the combination of control elements regulates gene action
Different combos of activators (transcription factors) makes different genes turn on
Different genes can be turned on by same activator

21. Cell-type specific transcription based on available activators
Albumin is a blood protein (made in liver)
Crystallin is the main protein in the lens of the eye (made in eye)

22. DIFFERENTIAL GENE EXPRESSION = DIFFERENT CELL TYPES
Cell differentiation – process by which cells become specialized in structure and function
Morphogenesis – process that gives an organism its form (shape)
Pattern formation – development of spatial organization in which tissues and organs are in their correct places
Positional information – molecular cues that control pattern formation
Homeotic genes – control pattern formation

23. Caused by a mutated homeotic gene

24. CANCER
Oncogenes- cancer causing genes in retroviruses
Proto-oncogenes – normal genes that code for proteins that stimulate cell growth and division
Tumor suppressor genes - make proteins that help prevent uncontrolled cell growth

25. Converting proto-oncogene into oncogene

26. Converting proto-oncogene into oncogene
Movement of DNA within a chromosome
May place a more active promoter near a proto-oncogene (= more cell division)
Amplification of a proto-oncogene
Point mutations in control element or proto-oncogene (= more expression or makes abnormal protein that doesn’t get degraded or is more active)

27. GENES INVOLVED IN CANCER
Ras gene – makes ras (G) protein that starts cascade reactions that initiate cell division
Mutations in Ras gene cause ~30% cancers
p53 tumor suppressor gene – “guardian of genome”
Activates p21 which halts cell cycle
Turns on genes to repair DNA
Activates suicide proteins that cause cell death (apoptosis)
Mutations in P53 gene cause ~50% cancer

30. Multistep Model of Cancer Development
Approximately half dozen changes have to occur at the DNA level for cancer to develop.
Need at least one oncogene and loss of tumor suppressor gene(s)
Most oncogenes are dominant and most tumor suppressor genes recessive so must knock out both alleles
Typically telomerase is activated

31. A multi-step model for the development of colorectal cancer

32. Inherited Predisposition to Cancer
15% colorectal cancers are inherited
Most from mutated APC gene (tumor suppressor gene)
5-10% breast cancers are inherited
Most with mutated BRCA1 and BRCA2
A woman with one mutant BRCA1 gene (tumor suppressor gene) has a 60% chance of getting breast cancer by age 50