Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

378 Chapter 7: Control of Gene Expression
bits
(A)
(C)
2
1
0
Nanog cis-regulatory sequence
transcription regulator
cis-regulatory sequence
in genome
dimer dimer heterodimer
recognized by the protein has increased from approximately 6 nucleotide pairs
to 12 nucleotide pairs, there are many fewer random occurrences of matching
sequences.
Heterodimers are often formed MBoC6 n7.201/7.09
from two different transcription regulators.
Transcription regulators may form heterodimers with more than one partner protein;
in this way, the same transcription regulator can be “reused” to create several
distinct DNA-binding specificities (see Figure 7–9C).
(B)
Figure 7–9 Transcription regulators and
cis-regulatory sequences. (A) Depiction
of the cis-regulatory sequence for Nanog,
a homeodomain family member that is
a key regulator in embryonic stem cells.
This “logo” form (see Figure 6–12) shows
that the protein can recognize a collection
of closely related DNA sequences and
gives the preferred nucleotide pair at each
position. Cis-regulatory sequences are
“read” as double-stranded DNA, but only
one strand typically is shown in a logo.
(B) Representation of the cis-regulatory
sequence as a colored box. (C) Many
transcription regulators form dimers
(homodimers) and heterodimers. In the
example shown, three different DNAbinding
specificities are formed from two
transcription regulators.
Transcription Regulators Bind Cooperatively to DNA
In the simplest case, the collection of noncovalent bonds that holds the above
dimers or heterodimers together is so extensive that these structures form obligatorily,
and never fall apart. In this case, the unit of binding is the dimer or heterodimer,
and the binding curve for the transcription regulator (the fraction of DNA
bound as a function of protein concentration) has a standard exponential shape
(Figure 7–10A).
In many cases, however, the dimers and heterodimers are held together very
weakly; they exist predominantly as monomers in solution, and yet dimers are
observed on the appropriate DNA sequence. Here, the proteins are said to bind to
DNA cooperatively, and the curve describing their binding is sigmoidal in shape
(Figure 7–10B). Cooperative binding means that, over a range of concentrations of
the transcription regulator, binding is more of an all-or-none phenomenon than
occupancy of DNA
(fraction bound)
1
cis-regulatory elements
occupancy of DNA
(fraction bound)
0 0
protein concentration
protein concentration
(A)
(B)
1
Figure 7–10 Occupancy of a cisregulatory
sequence by a transcription
regulator. (A) Noncooperative binding by a
stable heterodimer. (B) Cooperative binding
by components of a heterodimer that are
predominantly monomers in solution. The
shape of the curve differs from that of (A)
because the fraction of protein in a form
competent to bind DNA (the heterodimer)
increases with increasing protein
concentration.