Page 57 - Academic Press Encyclopedia of Physical Science and Technology 3rd Molecular Biology

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Encyclopedia of Physical Science and Technology EN006H-655 June 29, 2001 21:21

506 Gene Expression, Regulation of

DNA sequence elements capable of binding transcrip-
tional activator or repressor proteins only tells us part
of the story, namely which factors have the capacity to
control promoter activity. However, actual RNA synthesis
requires a complex interplay between UAS-binding fac-
tors and the chromatin or the chromatin remodeling factors
that have positive or negative effects on promoter activity.

2. Regulation of Transcription Factor Activity
The activity of a UAS-binding transcription factor is
subjected to a posttranslational regulation. There are in
principle three ways that the activity of an UAS-binding
transcription factor may be tuned (Fig. 3); covalent (like
phosphorylation) or noncovalent (like hormone binding)
modification of the UAS-binding factor, or variation of
the subunit composition (like binding of an inhibitory pro-
tein). These mechanisms may be used individually or in
combination with other mechanisms to regulate transcrip-
tion. To illustrate the flexibility of transcriptional con-
trol in eukaryotic cells two examples are presented. The
first example concerns the activation of steroid hormone-
dependent gene transcription (Fig. 4). Steroid hormones
are a group of substances derived from cholesterol which
exert a wide range of effects on processes such as growth,
metabolism, and sexual differentiation. A prototypical
member of a steroid hormone-inducible transcription fac-
tor is the glucocorticoid receptor (GR). In the absence of
hormone this receptor is found as a monomer in the cy-

FIGURE 4 A schematic drawing showing the activation of gluco-
corticoid receptor (GR) by steroid hormone binding, which results
in the dissociation of the cytoplasmic GR–hsp90 complex, fol-
lowed by GR dimerization and translocation of GR to the nucleus.

toplasm complexed to the heat-inducible hsp90 protein.
Treatment with steroid hormones results in the release
of GR from hsp90, which renders GR free to dimer-
ize and move to the nucleus, where it binds to its cog-
nate DNA sequence element and activates transcription
(Fig. 4). In addition to inducing a dissociation of the re-
ceptor from hsp90, ligand binding also induces a confor-
mational change in the activation domain of GR, such
FIGURE 3 Three common mechanisms to regulate transcription that the activation domain binds transcriptional coacti-
factor activity. vator proteins that stimulate transcription. Interestingly,