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Regulation of Gene
Expression
Chapter 8
You will not be responsible for:
Specific DNA binding motifs
Specific examples of combinational
control
Patterning of Drosophila
development
Questions in this chapter you should be able to answer:
Chapter 8- #s1 – 6, 8, 9,12,13
Gene Regulation
1
Why and when does gene
regulation occur?
Differentiation
Development
Response
‘Housekeeping’ vs
Inducible genes
Gene Regulation
2
Where in the flow of
information from DNA to
protein does regulation
occur?
Transcriptional
Post-transcriptional 
(influence activation
of RNA polymerase)
Gene Regulation
3
What is an operon?
What are the two major types of gene regulatory proteins?
Repressors
Activators
Gene Regulation
4
How do DNA binding proteins recognize appropriate sequences?
Homeodomain
TATA-binding protein
Zinc finger
Gene Regulation
Leucine zipper
5
How does a repressor protein
function?
The “tryptophan operon” model
trp operon encodes genes for
tryptophan synthesis
Promoter element
Operator element
Repressor protein
Gene Regulation
6
How does an gene activating
protein function?
e.g., Catabolic
Activator Protein
(CAP)
Question 8-10
The ArgR repressor protein regulates genes involves in arginine biosynthesis by
binding to promotor sequences. Would you expect that binding of Arg to the ArgR
protein would increase or decrease its affinity for the regulatory sequence?
Gene Regulation
7
How can gene repression and activation
yield subtle regulatory control?
e.g., the ‘lac operon’
Encodes genes for
Lactose breakdown
CAP binds cAMP
high GLU = low cAMP
low GLU = high cAMP
Virtual Cell Animation
Lac operon
Gene Regulation
8
How is transcriptional control
different in eukaryotes?
… 3 mechanisms
Remember…
1) Chromatin Remodeling
DNA supercoiling
Histone modifications
Gene Regulation
9
Also remember…
2) General transcription factors
TATA box associated
RNA polymerase II associated
Add to this…
3) Enhancer and silencer
Elements
Combinational control
Gene Regulation
10
How far away from a gene can
a gene enhancer function?
Through genetic engineering you engineer
cells with varying distance between a
gene and its enhancer.
For each cell line, you measure the level
of mRNA expression, and get the pattern
shown in this figure.
A. Why does expression initially
increase as the distance increases?
B. Why does enhance activity oscillate
~ every 10 bases?
C. Why does oscillation eventually
dampen out?
D. Why does enhancer activity slowly
decline?
Gene Regulation
11
“Epigenetic” control
-- transmission of regulatory states
to subsequent cell generations
FEED_FORWARD
GENE REGULATION
1) Feed-forward transmission
of gene regulators
2) Histone modification
**** see question 5-13 ****
HISTONE
MODIFICATION
3) Cytosine methylation
-- “Genomic imprinting”
Gene Regulation
12
Post-Transcriptional
Control Mechanisms
Function after transcription
begins or is completed
RNA interference
Ubiquitylation
 proteosomes
1) Control of (alternative)
exon/intron splicing
2) Riboswitches
RNA 5’-UTR
binding
proteins
1) Allosteric regulation
2) Covalent regulation
3) etc.
Gene Regulation
13
What is RNA interference
“RNAi” ?
Targeted degradation of mRNAs
dsRNA precursors
-- processed by dicer enzyme
-- yield short (~21 base) RNA
From exogenous sources
-- yield siRNA
-- protection against pathogens
From endogenous
-- yield miRNA
-- often in introns
-- gene regulation
RISC
-- “RNA Induced Silencing Complex
-- mi/siRNA ‘guides’ it to target mRNAs
Gene Regulation
14
RNA interference has many
research applications
Targeting of specific mRNAs
Short hairpin RNAs (shRNA)
shRNA libraries available
Future therapeutic applications?
Gene Regulation
15