594
chapter 26
Regulation of Gene Expression
molecules each of which encodes one protein. Regulation
of synthesis of the primary transcripts simultaneously reg-
ulates synthesis of all the gene products.
In prokaryotes, gene expression fluctuates because bac-
teria must be able to respond rapidly to a changing en-
vironment. However, in the differentiation of cells of the
higher eukaryotes, changes in gene expression are usually
irreversible, as in the differentiation of a muscle cell from
a precursor cell. By changing the number of copies of a
gene during differentiation, eukaryotic cells can regulate
levels of gene expression.
26.2 Gene Regulation in Prokaryotes
Several common patterns of transcription regulation have
been observed in bacteria. The particular pattern depends
on the type of metabolic activity of the system being reg-
ulated. For example, in a catabolic (degradative) pathway,
the concentration of the substrate for the first enzyme
in the pathway often determines whether all the enzymes in
the pathway are synthesized. In contrast, the final product
is often the regulatory substance in a biosynthetic pathway.
In the simplest mode, absence of an end product stimu-
lates transcription and presence of an end product inhibits
it. Even for a gene in which a single type of protein is
synthesized from monocistronic mRNAs, the protein may
“autoregulate” itself in the sense that the transcriptional
activity of the promoter is determined directly by the con-
centration of the protein. The molecular mechanisms for
each regulatory system vary considerably but usually fall
in one of two major categories—negative regulation and
positive regulation.
In
negative regulation,
an inhibitor, which keeps tran-
scription turned off, is present in the cell and an anti-
inhibitor—an inducer—is needed to turn the system on.
In
positive regulation,
an effector molecule (which may
be a protein, small molecule, or molecular complex) acti-
vates a promoter. Negative and positive regulation are not
mutually exclusive, and some degradative pathways, such
as the utilization of lactose in
E. coli,
are both positively
and negatively regulated.
Lactose (lac) Operon
The prototype for negative regulation is the system in
E. coli
for metabolizing lactose (lac) (Figure 26-1). The
key chemical reaction carried out by the lac system is a
cleavage of lactose to galactose and glucose. This reac-
tion enables bacteria to utilize lactose as a carbon source
when glucose is not available. The regulatory mechanism
of the lac system, known as the
operon model,
was the
(a)
Repressor
Operator
gene
Promoter
Structural genes
_____A
____
H
L
(b)
i
D[
y
1
a
1
4
Repressor binds to the operator
and prevents transcription ot
i. y
.
and a genes
i
m RNA
1
A
_
j
W
Repressor
I
P
i3
/
1
r
1
a
1
\
------►
I
mRNA
*
/(-Gaiactosidase
Permease
Transacetyiase
Inducer-repressor complex
which cannot bind to the operator
FIG U R E 26-1
(a) Genetic map of the lac operon, not drawn to scale; the p and o sites are
actually much smaller than the genes, (b) Diagram of the lac operon in (I)
repressed and (II) induced states. The inducer alters the shape of the
repressor, so the repressor can no longer bind to the operator.
first system described in detail, and it defines most of the
terminology and concepts in current use. The principal
regulatory features of the lac operon are as follows:
1. The products of two genes are required for lactose
utilization. The
lacz
gene encodes an enzyme,
/3-galactosidase, that degrades lactose; the
lacy
gene
encodes a protein, lac permease, needed to transport
lactose and concentrate it within the cell. A third gene,
laca,
encodes an enzyme that participates in lactose
metabolism only in certain circumstances; some
lactose-fermenting bacteria do not have the
laca
gene,
and it is not essential for lactose utilization in bacteria.
2. Lac enzymes are encoded in a single polycistronic
mRNA molecule (lac mRNA), and enzyme levels are
regulated by controlling synthesis of that mRNA.
3. Synthesis of lac mRNA is determined by the activity
of a specific regulatory protein—the lac repressor.
This protein is encoded in the
laci
gene, which is
transcribed in a monocistronic mRNA molecule
distinct from lac mRNA. When the repressor is active,
