1. Regulation of Gene Activity and Gene Mutations
Chapter 15
Regulation of Gene Activity and Gene Mutations

2. 15.1 Prokaryotic Regulation
Operons regulate genes in prokaryoes
operon model proposed by Francois Jacob and Jacques Monad to explain gene regulation in prokaryotes
operon: group of structural and regulating genes that function as a single unit

3. 15.1 Prokaryotic Regulation
Operons regulate genes in prokaryoes, cont.
operon, cont.
regulator gene: encodes a protein called repressor that controls the operon
parts of an operon:
promoter: where RNA polymerase binds to start transcription (signals start of a gene)

4. The parts of an operon

5. Parts of an Operon Regulator Gene Promoter Structural Genes Terminator
RNA
Polymerase
Repressor
DNA
Operator
When Repressor is at the operator,
RNA Polymerase can’t attach to the Promoter and transcription is blocked

6. 15.1 Prokaryotic Regulation
Operons regulate genes in prokaryoes, cont.
operon, cont.
parts of an operon, cont.
operator: where an active repressor binds to prevent transcription by overlapping the promoter (preventing RNA polymerase binding)

7. 15.1 Prokaryotic Regulation
Operons regulate genes in prokaryoes, cont.
operon, cont.
parts of an operon, cont.
structural genes: one to several genes coding for enzymes of a metabolic pathway
terminator: transcription stop sequence

8. 15.1 Prokaryotic Regulation
The trp Operon
usually in the “on” position
five structural genes code for five enzymes involved in synthesis of amino acid tryptophan
the regulator codes for a repressor that ordinarily cannot attach to the operator

9. 15.1 Prokaryotic Regulation
The trp Operon, cont.
regulation
if tryptophan is already present, cell does not need tryptophan-synthesizing enzymes
tryptophan binds to repressor, causing a change in shape
tryptophan is a corepressor
repressor binds to operator
therefore trp operon is a repressible operon

10. Fig The trp operon

11. Negative feedback of trp metabolism

12. 15.1 Prokaryotic Regulation
The lac Operon
usually in the “off” position
three structural genes code for three enzymes involved in lactose metabolism
one breaks lactose into glucose and galactose
another allows lactose to enter the cell
the regulator codes for a repressor that ordinarily binds to operon

13. 15.1 Prokaryotic Regulation
The lac Operon, cont.
regulation
when lactose is absent, cell does not need lactose-metabolizing enzymes
when glucose is absent and lactose is present, lactose binds to the repressor, causing a change in shape
lactose is an inducer
repressor cannot bind to operator

14. Fig The lac operon

15. 15.1 Prokaryotic Regulation
The lac Operon, cont.
regulation, cont.
therefore lac operon is an inducible operon
cAMP/CAP system
when glucose is present, more ATP is available (and less cAMP)
when glucose is absent, cyclic AMP (cAMP) accumulates
cAMP: derived from ATP; has one phosphate attached in two places

16. Cyclic AMP

17. 15.1 Prokaryotic Regulation
The lac Operon, cont.
cAMP/CAP system, cont.
cAMP binds to catabolite activator protein (CAP)
complex attaches to CAP binding site next to lac promoter
DNA bends to better expose promoter to RNA polymerase, increasing the rate of transcription

18. Fig. 15.3a CAP activity, no glucose

19. Fig. 15.3b CAP activity, glucose

20. 15.1 Prokaryotic Regulation
The lac Operon, cont.
cAMP/CAP system, cont.
when [lactose] = 0, no transcription
when [lactose] = high and ATP:cAMP = high, minimum transcription
when [lactose] = high and ATP:cAMP = low, maximum transcription

21. 15.2 Eukaryotic Regulation
Eukaryotic DNA differs from prokaryotic DNA in key ways
Prokaryotes
Eukaryotes
circular chromosomes
linear chromosomes
one chromosome
many chromosomes
no proteins
many proteins
not repetitive
highly repetitive
regulated by operons
regulation more complex

22. Fig. 15.4 Eukaryotic gene regulation

23. 15.2 Eukaryotic Regulation
Eukaryotes possess a variety of mechanisms to regulate gene expression
Chromatin Structure
1. chromatin consists of DNA (2 nm) wound around histones
histones help organize DNA and prevent access to DNA
2. each core of eight histones (and DNA) forms a nucleosome (11 nm)

24. 15.2 Eukaryotic Regulation
Chromatin Structure, cont.
3. nucleosomes coil (30 nm)
4. euchromatin: looped chromatin (300 nm)
state most chromatin is in
5. heterochromatin: condensed chromatin (700 nm)
inactive
6. condensed chromosome (1,400 nm)

25. Fig. 15.5a Levels of chromatin struct.

26. Fig. 15.5b Hetero- and euchromatin

27. Fig. 15.5c A nucleosome

28. 15.2 Eukaryotic Regulation
Chromatin Structure, cont.
Barr bodies are inactivated X chromosomes in cells of mammalian females
do not produce gene products
in heterochromatin form
X-inactivation is random
epigenetic inheritance is the transmission of genetic information outside the coding sequence of a gene

29. Fig X-inactivation

30. Fig. 15.6a X-inactivation

31. Fig. 15.6b Tortoiseshell cat

32. 15.2 Eukaryotic Regulation
Transcriptional Control
no operons
Transcription Factors and Activators
transcription factors: proteins that regulate transcription
bind to promoter
attract and bind RNA polymerase
transcription activators: also promote transcription
bind to enhancer
bridged by mediators

33. Fig. 15.8 Initiation of transcription

34. 15.2 Eukaryotic Regulation
Transcriptional Control, cont.
Transposons
transposons are DNA sequences that can move within and between chromosomes
they usually decrease or shut down gene expression

35. Fig. 15B,C Indian corn

36. 15.2 Eukaryotic Regulation
Posttranscriptional Control
mRNA processing
introns removed and exons spliced
speed with which mRNA leaves the nucleus
Translational Control
often involves 5’ cap or 3’ poly-A tail
Posttranslational Control
inc. protein activation or destruction

37. Fig mRNA processing

38. Genetic mutations can dramatically affect phenotype
Effect of Mutations on Protein Activity
point mutation: change in a single DNA nucleotide; could change amino acid
frameshift mutation: nucleotides are inserted or deleted from DNA; could change every codon!

39. Fig Point mutation

40. Mutations

41. Effect of Mutations…, cont.
15.3 Genetic Mutations
Effect of Mutations…, cont.
faulty or nonfunctional proteins can have a dramatic effect on phenotype
examples:
hemophilia
phenylketonuria
albinism
cystic fibrosis
androgen insensitivity syndrome

42. 15.3 Genetic Mutations Carcinogenesis
tumor suppressor genes and proto-oncogenes often code for transcription factors or proteins that control transcription factors
example: p53 (tumor suppressor gene) is often mutated in human cancers; p53 is a transcription factor often involved in turning on genes that produce cell cycle inhibitors

43. Fig Carcinogenesis

44. 15.3 Genetic Mutations Causes of Mutations spontaneous
spontaneous mutations due to DNA replication errors are rare
environmental
mutagens increase the chances of a mutation
carcinogens are mutagens that cause cancer
chemicals, smoke, X-rays, gamma rays, UV light

45. Fig. 15.13 Results of mutations

46. Result of UV radiation exposure