Transcript BioH Control over Genes Ch14

BioH Chapter 14 –
Control over Genes
Control of Gene Expression
Cells are selective about which genes they require
This depends upon:
 Cell type
 Specific cell activity at the moment of need
 External chemical signals received
 Built-in internal chemical signals
Two main systems of control:
 Negative feedback
 Positive feedback
Systems use: regulatory proteins, hormones, other
molecules
Bacterial Cell Gene Control
Escherichia coli
Negative transcription control – lac operon
Promoter sequence – base sequence signaling the start of a gene
Operator sequence – between promoter & genes, binding site for repressor
Repressor protein – regulatory protein that can block transcription of genes
Operon – arrangement where promoter and operator control more than one
gene
Low lactose concentration – Repressor is free to block
transcription (RNA polymerase cannot bind)
With low concentrations of lactose, the regulator gene produces
repressor proteins that bind at the operator site, blocking the promoter
sequence form starting the production of lactose digesting enzymes.
(Negative control)
High lactose concentration – lactose induces transcription by binding
to the repressor (distorting the shape) so that is cannot bind to the
operator site. The promoter is exposed and transcription occurs
producing lactose-digesting enzymes.
Negative transcription control summary
(E.coli lactose operon)
• Low lactose concentration does not allow lactose-degrading
enzymes to be produced by allowing the repressor protein to bind at
the operator site, preventing RNA polymerase from binding.
• High lactose concentration allows some lactose molecules to bind to
the repressor proteins, keeping them from binding to the operator.
This allows RNA polymerase to bind to the promoter site, causing
transcription of the lactose-degrading enzymes. They are produced
only when there is a high enough concentration of lactose.
Positive transcription control summary
(E.coli and glucose)
E. Coli pays far more attention to glucose than to lactose, producing
more enzymes for glucose digestion and at a much faster rate. In fact,
the lactose operon isn’t used much – unless glucose is absent.
When no glucose is present in the bacterium, CAP, an activator protein,
acts upon the lac operon by helping RNA polymerase to bind to the
promoter sequence.
• CAP is activated by cAMP (produced from ATP, with low
concentrations of glucose)
• High glucose concentration
– Low cAMP
– CAP does not adhere to lactose promoter
– Almost no lactose degenerating enzymes
• Low glucose concentration with high lactose conentration
– cAMP accumulates
– CAP adheres to lactose promoter, allowing lactose metabolizing
enzymes to form
Eukaryotic cell gene controls
Cell Differentiation
Even though all somatic
cells contain the same
DNA as found in the
fertilized egg, nearly all
cells become specialized
in composition, structure
and function = cell
differentiation. So, genes
specifying proteins need
to be very specific for the
cell in which they occur.
It is estimated that only
5-10% of the genes
found in a cell are used
at any given time.
Eukaryotic Gene Control
Signaling Mechanisms - Hormones
 Have positive or negative control in target cells
 Modify enhancers – base sequences in DNA that act
as binding site for specific activator proteins
Eukaryotic Cell Gene Control
Overview
 In multicellular organisms, gene controls underlie
basic, short-term housekeeping cellular tasks as well
as more intricate long-term patterns of bodily growth
and development.
As cells differentiate, some suppress certain genes
not necessary for cell function.
Hormones and other environmental signals
influence gene expression inside the cells.
Levels of Gene Expression
Control
 Basic, “housekeeping” tasks – under
control of positive system control
(continuous and low levels)
 Homeostatic systems – much more
complex and involve many cells –
under fluctuating positive and negative
systems control
 Both before and after transcription
occurs
 All control systems must be highly
coordinated to allow multicellular
interaction
Out of control
Cells go through their life cycles in very controlled/regulated
manner
Regulatory proteins control
• onset of activities
• timing
• amount of activity
• response to external &
internal stimuli
If a cell lacks these proteins (due
to mutated genes not transcribing
correct, or any, molecules), then
the cell is deprived of crucial
proteins – may result in cancer
Normal Cell Cycle
Protein kinases –
enzymes that control
passage of cells
through life cycle by
controlling phosphate
group attachment.
Operate between
G1 and S phase and
G2 to mitosis
Cancer Cell Characteristics
 Cell’s plasma membrane & cytoplasm change dramatically
• Membrane is more permeable
• Proteins lost or altered, abnormal ones are formed
• Cytoskeleton disorganizes, shrinks, or both
• Enzyme activity accelerates
 Cancer cells grow & divide abnormally
• Overpopulation controls are lost
• Cell populations reach high densities
• Enzymes trigger increased blood vessels in area
Cancer cells do not adhere to each other as normal cells do
• Inability to stay anchored to proper tissues
Cancer cells are lethal – if not eradicated, the organism eventually
dies
Cell growth out of control
• Tumors
– Do NOT respond to normal cell growth control (cell surface
enzyme malfunction)
– As long as conditions are favorable, cells grow and divide
– Do NOT have correct repair machinery (DNA/RNA polymerase,
ligase)
• Benign Tumor
– Slow growth
– Usually stay confined to original growth site
• Malignant Tumor
– Rapid growth
– Exhibits metastasis
Benign Tumors
Malignant Tumors
Normal Mole
Malignant moles
Cysts
Cancerous cell progression
Malignant cancers
The three most common cancers in men in the United
States are:
– Prostate cancer
– Lung cancer
– Colon cancer
In women in the United States, the three most common
cancers are:
– Breast cancer
– Colon cancer
– Lung cancer