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caryotic gene by RNA polymerase II. To begin transcription, RNA polymerase requires a num
Figure 7-43. Activation of transcription initiation in eucaryotes by recruitment of the
eucaryotic RNA polymerase II holoenzyme complex. (A) An activator protein bound in
proximity to a promoter attracts the holoenzyme complex to the promoter. According to
this model, the holoenzyme (which contains over 100 protein subunits) is brought to the
promoter separately from the general transcription factors TFIID and TFIIA. The “broken”
DNA in this and subsequent figures indicates that this portion of the DNA molecule can
be very long and of variable length. (B) Diagram of an in vivo experiment whose
outcome supports the holoenzyme recruitment model for gene activator proteins. The
DNA-binding domain of a protein has been fused directly to a protein component of the
mediator, a 20-subunit protein complex which is part of the holoenzyme complex, but
which is easily dissociable from the remainder of the holoenzyme. When the binding site
for the hybrid protein is experimentally inserted near a promoter, transcription initiation is
polymerase II in a eucaryotic cell. Transcription initiation in vivo requires the presence of tra
Figure 7-45. Local alterations in chromatin structure directed by eucaryotic gene
activator proteins. Histone acetylation and nucleosome remodeling generally render the
DNA packaged in chromatin more accessible to other proteins in the cell, including those
required for transcription initiation. In addition, specific patterns of histone modification
directly aid in the assembly of the general transcription factors at the promoter (see
Figure 7-46). Transcription initiation and the formation of a compact chromatin structure
can be regarded as competing biochemical assembly reactions. Enzymes that increase,
even transiently, the accessibility of DNA in chromatin will tend to favor transcription
initiation (see Figure 4-34).
TBP (TATA-binding protein) bound to DNA. The TBP is the subunit of the general transcript
ical eucaryotic gene. The promoter is the DNA sequence where the general transcription fac
g the properties of insulators. Insulators both prevent the spread of heterochromatin (right-h
atory system that determines the mode of growth of bacteriophage lambda in the E. coli hos
f mutations affecting the three types of segmentation genes. In each case the areas shaded
can coordinate the expression of several different genes. The action of the glucocorticoid re
Figure 7-56. Distribution of the gene regulatory proteins responsible for ensuring that
eve is expressed in stripe 2. The distributions of these proteins were visualized by
staining a developing Drosophila embryo with antibodies directed against each of the
four proteins (see Figures 7-52 and 7-53). The expression of eve in stripe 2 occurs only
at the position where the two activators (Bicoid and Hunchback) are present and the two
repressors (Giant and Krüppel) are absent. In fly embryos that lack Krüppel, for
example, stripe 2 expands posteriorly. Likewise, stripe 2 expands posteriorly if the DNAbinding sites for Krüppel in the stripe 2 module (see Figure 7-55) are inactivated by
mutation and this regulatory region is reintroduced into the genome. The eve gene itself
encodes a gene regulatory protein, which, after its pattern of expression is set up in
seven stripes, regulates the expression of other Drosophila genes. As development
proceeds, the embryo is thus subdivided into finer and finer regions that eventually give
rise to the different body parts of the adult fly, as discussed in Chapter 21. This example
from Drosophila embryos is unusual in that the nuclei are exposed directly to positional
cues in the form of concentrations of gene regulatory proteins. In embryos of most other
organisms, individual nuclei are in separate cells, and extracellular positional information
must either pass across the plasma membrane or, more usually, generate signals in the
2 unit. The segment of the eve gene control region identified in the previous figure contains
modular construction of the eve gene regulatory region. (A) A 480-nucleotide-pair piece of t
four gene regulatory proteins in an early Drosophila embryo. At this stage the embryo is a s
encoded by the even-skipped (eve) gene in a developing Drosophila embryo. Two and one
y proteins in muscle development. (A) The effect of expressing the MyoD protein in fibroblas
Figure 7-36. Summary of the mechanisms by which specific gene regulatory proteins
control gene transcription in procaryotes. (A) Negative regulation; (B) positive regulation.
Note that the addition of an “inducing” ligand can turn on a gene either by removing a
gene repressor protein from the DNA (upper left panel) or by causing a gene activator
protein to bind (lower right panel). Likewise, the addition of an “inhibitory” ligand can turn
off a gene either by removing a gene activator protein from the DNA (upper right panel)
or by causing a gene repressor protein to bind (lower left panel).
polymerase II in a eucaryotic cell. Transcription initiation in vivo requires the presence of tran
Figure 7-49. Five ways in which eucaryotic gene repressor proteins can operate. (A)
Gene activator proteins and gene repressor proteins compete for binding to the same
regulatory DNA sequence. (B) Both proteins can bind DNA, but the repressor binds to
the activation domain of the activator protein thereby preventing it from carrying out its
activation functions. In a variation of this strategy, the repressor binds tightly to the
activator without having to be bound to DNA directly. (C) The repressor interacts with an
early stage of the assembling complex of general transcription factors, blocking further
assembly. Some repressors also act at late stages in transcription initiation, for example,
by preventing the release of the RNA polymerase from the general transcription factors.
(D) The repressor recruits a chromatin remodeling complex which returns the
nucleosomal state of the promoter region to its pre-transcriptional form. Certain types of
al gene control for development. Combinations of a few gene regulatory proteins can genera
ow a positive feedback loop can create cell memory. Protein A is a gene regulatory protein th
gene in precursor cells of the leg triggers the development of an eye on the leg. (A) Simplifi
ecify eye development in Drosophila. toy (twin of eyeless) and ey (eyeless) encode similar
ulator-binding protein on polytene chromosomes. A polytene chromosome (see pp. 218–220