Prokaryotic Regulation

advertisement
Chapter 15
Gene Regulation
Gene Regulation
Outline
Prokaryotic Regulation
trp Operon
lac Operon
Eukaryotic Regulation
Transcriptional Control
Posttranscriptional Control
Translational Control
Posttranslational Control
Genetic Mutations
Cancer
2
Gene Regulation
Prokaryotic Regulation:
The Operon Model
Operon consist of three components
Promoter
- DNA sequence where RNA polymerase first
attaches
- Short segment of DNA
Operator
- DNA sequence where active repressor binds
- Short segment of DNA
Structural Genes
- One to several genes coding for enzymes of a
metabolic pathway
- Translated simultaneously as a block
- Long segment of DNA
3
Repressible Operons:
The trp Operon
Gene Regulation
The regulator codes for a repressor
If tryptophan (an amino acid) is absent:
Repressor is unable to attach to the operator
(expression is normally “on”)
RNA polymerase binds to the promoter
Enzymes for synthesis of tryptophan are produced
If tryptophan is present:
Combines with repressor as corepressor
Repressor becomes functional
Blocks synthesis of enzymes and tryptophan
4
The trp Operon
5
Inducible Operons:
The lac Operon
Gene Regulation
6
The regulator codes for a repressor
If lactose (a sugar that can be used for food) is
absent:
Repressor attaches to the operator
Expression is normally “off”
If lactose is present:
It combines with repressor and renders it unable to
bind to operator
RNA polymerase binds to the promoter
The three enzymes necessary for lactose catabolism
are produced
The lac Operon
7
Action of CAP
8
Gene Regulation
Eukaryotic Regulation
A variety of mechanisms
Five primary levels of control:
Nuclear levels
- Chromatin Packing
- Transcriptional Control
- Posttranscriptional Control
Cytoplasmic levels
- Translational Control
- Posttranslational Control
9
Regulation of Gene Expression:
Levels of Control in Eukaryotes
10
Gene Regulation
11
Chromatin Structure
Eukaryotic DNA associated with histone
proteins
Together make up chromatin
As seen in the interphase nucleus
Nucleosomes:
DNA wound around balls of eight molecules of
histone proteins
Looks like beads on a string
Each bead a nucleosome
The levels of chromatin packing determined
by degree of nucleosome coiling
Levels of Chromatin Structure
12
Gene Regulation
Chromatin Packing
Euchromatin
Loosely coiled DNA
Transcriptionally active
Heterochromatin
Tightly packed DNA
Transcriptionally inactive
Barr Bodies
Females have two X chromosomes, but only one is
active
Other is tightly packed along its entire length
Inactive X chromosome is Barr body
13
X-Inactivation in Mammalian Females 14
Gene Regulation
15
Transcriptional Control
Transcription controlled by proteins called
transcription factors
Bind to enhancer DNA
Regions of DNA where factors that regulate
transcription can also bind
Always present in cell, but most likely have to
be activated before they will bind to DNA
Lampbrush Chromosomes
16
Initiation of Transcription
17
Gene Regulation
18
Posttranscriptional Control
Posttranscriptional control operates on primary
mRNA transcript
Given a specific primary transcript:
Excision of introns can vary
Splicing of exons can vary
Determines the type of mature transcript that leaves
the nucleus
May also control speed of mRNA transport from
nucleus to cytoplasm
Will affect the number of transcripts arriving at rough
ER
And therefore the amount of gene product realized
per unit time
Processing of mRNA Transcripts
19
Gene Regulation
20
Translational Control
Translational Control - Determines degree to
which mRNA is translated into a protein
product
Presence of 5′ cap
Length of poly-A tail on 3′ end
Posttranslational Control - Affects the activity
of a protein product
Activation
Degradation rate
Effect of Mutations on
Protein Activity
Gene Regulation
21
Point Mutations
Involve change in a single DNA nucleotide
Changes one codon to a different codon
Affects on protein vary:
- Nonfunctional
- Reduced functionality
- Unaffected
Frameshift Mutations
One or two nucleotides are either inserted or deleted
from DNA
Protein always rendered nonfunctional
- Normal :
- After deletion:
- After insertion:
THE CAT ATE THE RAT
THE ATA TET HER AT
THE CCA TAT ETH ERA T
Point Mutation
22
23
Faulty Proteins = Genetic Disorders
Examples:
Sickle cell anemia
Hemophilia
PKU
Albinism
Huntington’s Disease
Androgen insensitivity
Androgen Insensitivity
24
25
Ea
A
(phe)
B
(tyr)
Eb
C
(Melanin)
Error in Enzyme a
26
27
The gene
that
produces
this
enzyme
is on
chromosome 9
28
The blood in the retina and iris
reflects red light, resulting in pink
29
Gene Regulation
30
Carcinogenesis
Development of cancer involves a series of
mutations
Proto-oncogenes – Stimulate cell cycle
Tumor suppressor genes – inhibit cell cycle
Mutation in oncogene and tumor suppressor
gene:
- Stimulates cell cycle uncontrollably
- Leads to tumor formation
Carcinogenesis
31
Achondroplasia and
Xeroderma Pigmentosum
32
Gene Regulation
Causes of Mutations
Replication Errors
1 in 1,000,000,000 replications
DNA polymerase
- Proofreads new strands
- Generally corrects errors
Environmental Mutagens
Carcinogens - Mutagens that increase the
chances of cancer
- Ultraviolet Radiation
- Tobacco Smoke
33
Gene Regulation
Review
Prokaryotic Regulation
trp Operon
lac Operon
Eukaryotic Regulation
Transcriptional Control
Posttranscriptional Control
Translational Control
Posttranslational Control
Genetic Mutations
Cancer
34
Ending Slide Chapter 15
Gene Regulation
Download