Essential Cell Biology 5th edition

How Transcription Is Regulated
271
degraded mRNA
DNA
1
transcriptional
control
RNA
transcript mRNA mRNA
2
RNA
processing
control
NUCLEUS CYTOSOL mRNA degradation protein
4
control
degradation
control
6
protein
3
mRNA
transport
and
localization
control
5
translation
control
7
active
protein
protein
activity
control
inactive
protein
degraded
protein
degraded, (5) selecting which mRNAs are translated into protein by ribosomes,
or (6) regulating how rapidly specific proteins are destroyed after
they have been made; in addition, the activity of individual proteins, once
they have been synthesized, can be further regulated in a variety of ways.
In eukaryotic cells, gene expression can be regulated at each of these
steps (Figure 8–3). For most genes, however, the control of transcription
(shown in step 1) is paramount. This makes sense ECB5 because e8.03/8.03 only transcriptional
control can ensure that no unnecessary intermediates are
synthesized. Thus it is the regulation of transcription—and the DNA and
protein components that determine which genes a cell transcribes into
RNA—that we address first.
Figure 8–3 Gene expression in eukaryotic
cells can be controlled at various steps.
Examples of regulation at each of these
steps are known, although for most
genes the main site of control is step 1:
transcription of a DNA sequence into RNA.
HOW TRANSCRIPTION IS REGULATED
Until 50 years ago, the idea that genes could be switched on and off was
revolutionary. This concept was a major advance, and it came originally
from studies of how E. coli bacteria adapt to changes in the composition
of their growth medium. Many of the same principles apply to eukaryotic
cells. However, the enormous complexity of gene regulation in organisms
that possess a nucleus, combined with the packaging of their DNA
into chromatin, creates special challenges and some novel opportunities
for control—as we will see. We begin with a discussion of the transcription
regulators (often loosely referred to as transcription factors), proteins
that bind to specific DNA sequences and control gene transcription.
Transcription Regulators Bind to Regulatory DNA
Sequences
Nearly all genes, whether bacterial or eukaryotic, contain sequences
that direct and control their transcription. In Chapter 7, we saw that the
promoter region of a gene binds the enzyme RNA polymerase and correctly
orients the enzyme to begin its task of making an RNA copy of
the gene. The promoters of both bacterial and eukaryotic genes include
a transcription initiation site, where RNA synthesis begins, plus nearby
sequences that contain recognition sites for proteins that associate with
RNA polymerase: sigma factor in bacteria (see Figure 7−9) or the general
transcription factors in eukaryotes (see Figure 7−12).
In addition to the promoter, the vast majority of genes include regulatory
DNA sequences that are used to switch the gene on or off. Some
regulatory DNA sequences are as short as 10 nucleotide pairs and act
as simple switches that respond to a single signal; such simple regulatory
switches predominate in bacteria. Other regulatory DNA sequences,
especially those in eukaryotes, are very long (sometimes spanning more
than 100,000 nucleotide pairs) and act as molecular microprocessors,