Transcript Regulation of Gene Expression - Zanichelli online per la scuola

David Sadava, David M. Hillis,
H. Craig Heller, May R. Berenbaum
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biologia.blu
Genetica, biologia molecolare ed
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Regulation of Gene
Expression
How Is Gene Expression Regulated in Prokaryotes?
Prokaryotes can make some proteins only when they
are needed.
E. coli in the human intestine must adjust quickly to
changes in food supply.
Glucose is the easiest sugar to metabolize.
If E.coli is grown with glucose but no lactose, no
enzymes for lactose conversion are produced.
If lactose is predominant and glucose is low, E.coli
synthesizes all enzymes after a short lag period.
How Is Gene Expression Regulated in Prokaryotes?
Structural genes specify primary protein structure—
the amino acid sequence.
The 3 structural genes for lactose enzymes are
adjacent on the chromosome and share a promoter,
forming the lac operon.
How Is Gene Expression Regulated in Prokaryotes?
An operon is a gene cluster with a single promoter.
A typical operon consists of:
•a promoter
•a terminator
•an operator
•Two or more structural genes
An operator—a short sequence between the
promoter and the structural genes; binds to
regulatory proteins.
How Is Gene Expression Regulated in Prokaryotes?
Three ways to control operon transcription:
• An inducible operon regulated by a repressor
protein
• A repressible operon regulated by a repressor
protein
• An operon regulated by an activator protein
How Is Gene Expression Regulated in Prokaryotes?
In the lac operon (inducible operon) the operator can
bind a repressor protein, which blocks transcription.
The repressor has 2 binding sites: one for the
operator, and one for the inducer (lactose).
When lactose is absent, the repressor prevents
binding of RNA polymerase to the promoter.
How Is Gene Expression Regulated in Prokaryotes?
When lactose is present, it binds to the repressor and
changes the repressor’s shape.
This prevents the
repressor from binding to
the operator, and then
RNA polymerase can bind
to the promoter, and the
genes are transcribed.
How Is Gene Expression Regulated in Prokaryotes?
The trp operon is a repressible system.
In these systems, the repressor isn’t bound to the
operator until a co-repressor binds to it.
The genes code for enzymes that catalyze synthesis
of tryptophan.
When there is enough tryptophan in the cell,
tryptophan binds to the repressor, which then binds to
the operator. Tryptophan is the co-repressor.
How Is Eukaryotic Gene Transcription Regulated?
In development of multicellular organisms, certain
proteins must be made at just the right times and in
just the right cells.
The expression of eukaryotic
genes must be precisely
regulated.
Regulation can occur at several
different points and the presence
of a nucleus physically
separates transcription and
translation.
Table 16.2
How Is Eukaryotic DNA Transcribed and the RNA Processed?
RNA splicing removes introns and splices exons
together.
snRNPs (small nuclear ribonucleoprotein particles)
bind to ends of introns at consensus sequences—
short DNA stretches that appear in many genes.
How Is Eukaryotic DNA Transcribed and the RNA Processed?
If the initial mRNA transcript (precursor or premRNA) is hybridized with DNA, there is full, linear,
loop-free hybridization.
The intervening regions
(introns) get transcribed
then sliced out of pre-mRNA
in the nucleus.
Only expressed sequences
(exons) reach the ribosome.
How Is Eukaryotic DNA Transcribed and the RNA Processed?
In the nucleus, pre-mRNA is modified:
•A 5′ cap is added at the 5′ end— also protects
mRNA from being digested by ribonucleases.
•A poly A tail is added at 3′ end— the tail assists in
export from the nucleus and is important for stability
of mRNA.
How Is Eukaryotic DNA Transcribed and the RNA Processed?
Mature mRNA leaves the nucleus through nuclear
pores.
A cap-binding protein complex binds to the 5′ cap and
to other proteins that are recognized by receptors at
the nuclear pore.
These proteins lead the mRNA through the pore;
unused pre-mRNAs stay in the nucleus.
How Do Epigenetic Changes Regulate Gene Expression?
Patterns of DNA methylation may include large
regions or whole chromosomes.
Two kinds of chromatin:
• Euchromatin—diffuse, light-staining; contains DNA
that is transcribed
• Heterochromatin—condensed, dark-staining,
contains genes not transcribed
How Do Epigenetic Changes Regulate Gene Expression?
Chromosomal protein alterations or chromatin
remodeling:
DNA is packaged with histone proteins into
nucleosomes. The DNA is inaccessible to RNA
polymerase and transcription factors.
The histones have “tails” with
positively charged amino acids,
which are attracted to negatively
charged DNA.
How Do Epigenetic Changes Regulate Gene Expression?
One type of heterochromatin is the inactive X
chromosome in mammals.
Males (XY) and females (XX) contain different
numbers of X-linked genes, yet for most genes
transcription rates are similar.
Early in development, one of the
X chromosomes in females is
inactivated.
How Is Eukaryotic Gene Transcription Regulated?
Promoters bind and orient RNA polymerase so that
the correct DNA strand is transcribed.
All promoters have consensus sequences that allow
them to be recognized by RNA polymerase.
Eukaryote promoters contain a sequence called the
TATA box—where DNA begins to denature.
Promoters also include regulatory sequences
recognized by transcription factors (regulatory
proteins).
How Is Eukaryotic Gene Transcription Regulated?
Some regulatory sequences are common to
promoters of many genes, other sequences are
specific to a few genes and are recognized by
transcription factors found only in certain tissues.
These play an important role in cell differentiation.
Enhancers: regulatory sequences that bind
transcription factors that activate transcription or
increase rate of transcription.
Silencers: bind transcription factors that repress
transcription.
How Is Eukaryotic Gene Transcription Regulated?
Most regulatory sequences are located near the
transcription start site.
Others may be located thousands of base pairs away.
Transcription factors may interact with the RNA
polymerase complex and cause the DNA to bend.
How Is Eukaryotic Gene Transcription Regulated?
Often there are many transcription factors involved.
The combination of factors present determines the
rate of transcription.
Although the same genes are present in all cells, the
fate of the cell is determined by which of its genes are
expressed.
How Is Eukaryotic Gene Transcription Regulated?
Cellular therapy is a new approach to diseases that
involve degeneration of one cell type.
Alzheimer’s disease involves degeneration of neurons
in the brain.
If other cells could be made to
differentiate into neurons, they
could be transferred to the patient.
How Is Eukaryotic Gene Expression Regulated After Transcription?
Alternative splicing: different mRNAs can be made
from the same gene.
Introns are spliced out; mature mRNAs have none.
Sometimes exons are spliced out too—resulting in
different proteins.
There are many
more human
mRNAs than
there are coding
genes.
How Is Eukaryotic Gene Expression Regulated After Transcription?
MicroRNAs(miRNAs): small RNAs produced by
noncoding regions of DNA.
The human genome has about 1,000 miRNA
encoding regions.
How Is Eukaryotic Gene Expression Regulated After Transcription?
Protein longevity regulation:
Proteins can be targeted for destruction when
ubiquitin attaches to it and attracts other ubiquitins,
forming a polyubiquitin chain.
The complex binds to a proteasome—a large
complex where the ubiquitin is removed and the
protein is digested by proteases.
How Is Eukaryotic Gene Expression Regulated After Transcription?
Some strains of human papillomavirus (HPV) add
ubiquitin to p53 and retinoblastoma proteins,
targeting them for degradation.
These proteins normally inhibit the cell cycle, so the
result of this HPV activity is unregulated cell division
(cancer).
What Are the Processes of Development?
Development: the process in which a multicellular
organism undergoes a series of progressive changes
that characterizes its life cycle.
In its earliest stages, a plant or animal is called an
embryo.
What Are the Processes of Development?
Four processes of development:
• Determination sets the fate of the cell
• Differentiation—the process by which different
types of cells arise
• Morphogenesis—organization and spatial
distribution of differentiated cells
• Growth—increase in body size by cell division and
cell expansion
How Does Gene Expression Determine Pattern Formation?
Fate of a cell is often determined by where the cell is.
Positional information often comes in the form of an
inducer called a morphogen, which diffuses from one
group of cells to another, setting up a concentration
gradient.
How Does Gene Expression Determine Pattern Formation?
Morphogens have been studied in the fruit fly
Drosophila melanogaster.
The head, thorax, and abdomen are each made of
several fused segments.
In the first 12 mitotic divisions there is no cytokinesis,
forming a multinucleate embryo.
Morphogens can diffuse easily in the embryo.
How Does Gene Expression Determine Pattern Formation?
The experiments revealed a cascade of gene
expression. Three gene classes are involved:
1. Maternal effect genes set up the major axes of
the egg.
Bicoid and nanos help
determine the anterior–
posterior axis of the
embryo.
How Does Gene Expression Determine Pattern Formation?
2. Segmentation genes determine boundaries and
polarity of each segment.
Three classes of genes act in sequence:
• Gap genes organize broad areas;
• Pair rule genes divide embryo into units of two
segments each;
• Segment polarity
genes determine
boundaries and
anterior–posterior
organization in individual
segments.
How Does Gene Expression Determine Pattern Formation?
3. Hox genes determine which organ will be made at
a given location.
They determine cell fate in each
segment.
Hox genes are on chromosome 3
in the same order as the segments
whose functions they determine.
Antennapedia mutation
Bithorax mutation
How Does Gene Expression Determine Pattern Formation?
Hox genes have a 180 base pair sequence called the
homeobox. It encodes a 60 amino acid sequence
called the homeodomain.
The homeodomain binds to specific DNA sequences
in the promoters of target genes.
This homeodomain is found in transcription factors
that regulate development in many other animals with
an anterior–posterior axis.
How Does Gene Expression Determine Pattern Formation?
Pattern formation: The process that results in the
spatial organization of tissues and organisms.
Linked to morphogenesis, creation of body form.
Morphogenesis involves cell division and
differentiation, as well as apoptosis (programmed
cell death).
In human embryos,
connective tissue links the
fingers and toes. Later, the
cells between the digits
die.
Adapted from
Life: The Science of Biology, Tenth Edition, Sinauer Associates, Sunderland, MA, 2014
Inc. All rights reserved