1. Chapter 15
Controls over Genes

2. Control over Genes
All organisms must regulate which genes are expressed at any given time
In multicellular organisms regulation of gene expression is essential for cell specialization 2

3. Differential Gene Expression
Almost all the cells in an organism are genetically identical
Differences between cell types result from differential gene expression
the expression of different genes by cells with the same genome
Abnormalities in gene expression can lead to diseases, including cancer 3

4. Signal NUCLEUS Chromatin
Figure 15.6a
Signal
NUCLEUS
Chromatin
Chromatin modification: DNA unpacking involving histone acetylation and DNA demethylation
DNA
Gene available for transcription
Gene
Transcription
RNA
Exon
Primary transcript
Figure 15.6a Stages in gene expression that can be regulated in eukaryotic cells (part 1: nucleus)
Intron
RNA processing
Tail
mRNA in nucleus
Cap
Transport to cytoplasm
CYTOPLASM 4

5. Protein processing, such as cleavage and chemical modification
Figure 15.6b
CYTOPLASM
mRNA in cytoplasm
Translation
Degradation
of mRNA
Polypeptide
Protein processing, such as cleavage and chemical modification
Active protein
Degradation of protein
Figure 15.6b Stages in gene expression that can be regulated in eukaryotic cells (part 2: cytoplasm)
Transport to cellular destination
Cellular function (such as enzymatic activity, structural support) 5

6. Gene Control which genes are expressed in a cell depends upon:
• type of cell
• internal chemical conditions
• external signals
• built-in control systems

7. Control Mechanisms negative control
regulatory proteins slow down or curtail gene activity
positive control
regulatory proteins promote or enhance gene activities

8. Controls in Eukaryotic Cells
Controls of eukaryotic gene expression

9. Mechanisms of Gene Control
Chromatin Structure
Transcriptional Control
Post Transcriptional Control
Translational Control
Post Translational Control

10. Chromatin Structure Chromatin a complex of DNA and protein
Chromosomes fit into the nucleus through an elaborate, multilevel system of packing
Chromatin undergoes striking changes in the degree of packing during the course of the cell cycle
packing used to keep genes turned off
can’t transcribed if highly condensed
histones regulate accessibility to DNA 10

11. Chromatin Structure euchromatin loosely bound DNA can be expressed
acetyl group
heterochromatin
tightly bound DNA
inactive
methylated

12. Unacetylated histones Acetylated histones
Nucleosome
Histone tails
Unacetylated histones
Acetylated histones
Figure 15.7 A simple model of the effect of histone acetylation 12

13. Epigenetic Inheritance
inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence
though chromatin modifications do not alter DNA sequence, they may be passed to future generations of cells
epigenetic modifications can be reversed, unlike mutations in DNA sequence
epigenetics 13

14. Transcriptional Control
controlled by DNA binding proteins
transcription factors
promoters
transposons
activators have two domains
one that binds DNA
a second that activates transcription
ehancers
increases transcription rates

15. Distal control element Enhancer TATA box
Promoter
Activators
Gene
DNA
Distal control element
Enhancer
TATA box
Figure A model for the action of enhancers and transcription activators (step 1) 15

16. Distal control element Enhancer TATA box
Promoter
Activators
Gene
DNA
Distal control element
Enhancer
TATA box
General transcription factors
DNA-
bending protein
Group of mediator proteins
Figure A model for the action of enhancers and transcription activators (step 2) 16

17. Distal control element Enhancer TATA box
Promoter
Activators
Gene
DNA
Distal control element
Enhancer
TATA box
General transcription factors
DNA-
bending protein
Group of mediator proteins
RNA polymerase II
Figure A model for the action of enhancers and transcription activators (step 3)
RNA polymerase II
Transcription initiation complex
RNA synthesis 17

18. Post Transcriptional Control
involves mRNA processing
splicing of exons together occur
determines how fast mRNA leaves the nucleus
specific zip code

19. Translational Control
determined by 5’, 3’
length of poly A tail
enzymes begin degradation of the poly-A tail
any influence on 3’ end can lead to destruction of mRNA

20. Post Translational Control
some proteins are not immediately active
some proteins are short lived
ex.) cyclin
Controls cell cycle
cell has proteasomes
carry out task of destroying proteins

21. X Chromosome Inactivation

22. X Chromosome Inactivation
A condensed X chromosome (Barr body) in the somatic cell nucleus of a human female

23. Most Genes Are Turned Off
Cells of a multi-celled organism rarely use more than 5-10 percent of their genes at any given time
The remaining genes are selectively expressed

24. Homeotic Genes Occur in all eukaryotes
Master genes that control development of body parts
Encode homeodomains (regulatory proteins)
Homeobox sequence can bind to promoters and enhancers

25. Gene Control in Prokaryotes
No nucleus separates DNA from ribosomes in cytoplasm
When nutrient supply is high, transcription is fast
Translation occurs even before mRNA transcripts are finished

26. Prokaryotic Versus Eukaryotic Gene Control

27. Negative control of the lactose operon
High Lactose
Negative control of the lactose operon

28. The Lactose Operon operator regulatory gene gene 1 gene 2 gene 3
transcription,
translation
promoter
lactose operon
repressor protein

29. Low Lactose Repressor binds to operator Binding blocks promoter
Transcription is blocked

30. CAP Exerts Positive Control
CAP is an activator protein
Adheres to promoter only when in complex with cAMP
Level of cAMP depends on level of glucose

31. Positive Control – High Glucose
There is little cAMP
CAP cannot be activated
The promoter is not good at binding RNA polymerase
The lactose-metabolizing genes are not transcribed very much

32. Positive Control – Low Glucose
cAMP accumulates
CAP-cAMP complex forms
Complex binds to promoter
RNA polymerase can now bind
The lactose-metabolizing genes are transcribed rapidly

33. Hormones Signaling molecules
Stimulate or inhibit activity in target cells
Mechanism of action varies
May bind to cell surface
May enter cell and bind to regulatory proteins
May bind with enhancers in DNA

34. Vertebrate Hormones Some have widespread effects
Somatotropin (growth hormone)
Others signal only certain cells at certain times
Prolactin stimulates milk production