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25.1 Control of Gene Expression
• Gene Expression in Bacteria
– Operon: A cluster of structural and regulatory genes
that acts as a unit.
• Sequences consists of:
– Promoter: A sequence of DNA where
transcription begins
– Operator: A sequence of DNA where a
repressor protein binds
25.1 Control of Gene Expression
• Gene Expression in Bacteria
– Example: The lac Operon in E. coli
• When lactose is absent:
– The regulator gene codes for a repressor that is normally
active
– A repressor protein binds to the operator
– RNA polymerase cannot transcribe the three structural
genes of the operon (the structural genes are not
expressed)
25.1 Control of Gene Expression
• Gene Expression in Bacteria
– Example: The lac Operon in E. coli
• When lactose is present:
– Lactose binds with the lac repressor
– Repressor is unable to bind to the operator
– Structural genes are transcribed
» Enzymes are produced
The lac Operon
25.1 Control of Gene Expression
• Gene Expression in Eukaryotes
– “Housekeeping Genes”
• Not finely regulated
• Products are always needed to some degree
25.1 Control of Gene Expression
• Gene Expression in Eukaryotes
– Levels of Gene Control
• Chromatin Structure
• Transcriptional Control
• Posttranscriptional control
• Translational control
• Posttranslational control
25.1 Control of Gene Expression
• Levels of Gene Control
– Chromatin Structure
• Chromatin packing is used to keep genes turned off
• Heterochromatin: inactive genes located within darkly
staining portions of chromatin ex: Barr body
• Euchromatin: loosely packed areas of active genes
– Euchromatin still needs processing before transcription occurs
– Chromatin remodeling complex pushes aside nucleosomes
X-inactivation
25.1 Control of Gene Expression
• Levels of Gene Control
– Transcriptional Control
• Most important level of control
• Enhancers and promoters on DNA are involved
– Transcription factors and activators are proteins which regulate
these sites
– Posttranscriptional Control
• Removal of introns and splicing of exons
• Different patterns of splicing can occur
25.1 Control of Gene Expression
• Levels of Gene Control
– Translational Control
• Differences in the poly-A tails and/or guanine caps may
determine how long a mRNA is available for translation
• Specific hormones may also effect longevity of mRNA
– Posttranslational Control
• Some proteins must be activated after synthesis
• Many proteins function only for a short time before they are
degraded or destroyed by the cell
Levels of Gene Control in Eukaryotes
25.1 Control of Gene Expression
• Transcription Factors and Activators
– Transcription Factors- proteins which help RNA
polymerase bind to a promoter
• Several transcription factors per gene form a transcription
initiation complex
– Help in pulling DNA apart and in the release of RNA
polymerase for transcription
– Transcription Activators- proteins which speed up
transcription
• Bind to an enhancer region on DNA
• Enhancer and promoter may be far apart
– DNA forms a loop to bring them close together
Transcription Factors and Activators
25.1 Control of Gene Expression
• Signaling Between Cells
– Cells are in constant communication
– Cell produces a signaling molecule that binds to a
receptor on a target cell
• Initiates a signal transduction pathway- series of
reactions that change the receiving cell’s behavior
– May result in stimulation of a transcription
activator
– Transcription activator will then turn on a gene
Signal Transduction Pathway
25.2 Cancer: A Failure of
Genetic Control
• Contact Inhibition: When cells come into contact with
neighboring cells, they stop dividing.
• Cancer cells lose contact inhibition and form tumors.
• The tumor is deemed noncancerous or benign if it stays
as a single mass.
• Cells are called cancerous when they invade
surrounding tissues.
• Cancer cells can travel through the bloodstream and the
lymph and develop into secondary tumors.
• Metastasis refers to cancer cells that have spread to
other parts of the body.
Development of Cancer
25.2 Cancer: A Failure of
Genetic Control
• Characteristics of Cancer Cells
– Cancer cells are genetically unstable.
– Cancer cells do not correctly regulate the cell cycle
– Cancer cells escape the signals for cell death.
– Cancer cells can survive and proliferate elsewhere in
the body.
25.2 Cancer: A Failure of
Genetic Control
• Characteristics of Cancer Cells
– Cancer cells are genetically unstable.
• Multiple mutations, chromosome aberrations and may be
present.
25.2 Cancer: A Failure of
Genetic Control
• Characteristics of Cancer Cells
– Cancer cells do not correctly regulate the cell cycle.
• Normal controls of the cell cycle do not work.
• The rate of cell division and the number of cells increase.
25.2 Cancer: A Failure of
Genetic Control
• Characteristics of Cancer Cells
– Cancer cells escape the signals for cell death.
• Cancer cells do not respond to signals for apoptosis
– Telomeres of cancer cells do not shorten.
25.2 Cancer: A Failure of
Genetic Control
• Characteristics of Cancer Cells
– Cancer cells can survive and proliferate elsewhere in
the body.
• As a tumor grows, it stimulates the formation of new blood
vessels to supply oxygen and nutrients to the cancerous
cells. This is called angiogenesis.
25.2 Cancer: A Failure of
Genetic Control
• Proto-oncogenes and Tumor Suppressor Genes
– Proto-oncogenes promote the cell cycle and prevent
apoptosis.
– Tumor suppressor genes inhibit the cell cycle and
promote apoptosis.
25.2 Cancer: A Failure of
Genetic Control
• Proto-oncogenes
– Mutate into cancer causing genes called oncogenes.
– An altered RAS protein is found in approximately 25%
of all tumors.
Activity of Ras Protein
25.2 Cancer: A Failure of
Genetic Control
• Tumor Suppressor Genes
– When these mutate, they no longer inhibit the cell
cycle.
– A gene called p53 normally prevents cell division if
there is damage to the DNA. If p53 mutates, the cells
may continue to divide indefinitely.
– About 1/2 of all human cancers have a mutation in
this gene.
Activity of p53 Tumor Suppressor
25.2 Cancer: A Failure of
Genetic Control
• Causes of Cancer
– Heredity
• Some types of cancer run in families
– Carcinogens
• Environmental agents that are mutagenic
• Radiation, some viruses, organic chemicals
25.2 Cancer: A Failure of
Genetic Control
• Diagnosis of Cancer
– Screening tests
• Pap smear, mammogram, colonoscopy
• Tumor marker tests
• Genetic tests
– Confirming diagnosis
• Biopsy, ultrasound, radioactive scans
Needle Biopsy of the Breast
25.2 Cancer: A Failure of
Genetic Control
• Treatment of Cancer
– Chemotherapy
– Radiation therapy
– Bone marrow transplant
– Future Treatments
• Vaccines,
• Antiangiogenic drugs