Page 58 - 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

Gene Expression, Regulation of 507

HSE is needed for recruitment of the RNA polymerase
to the heat-shock promoter. The binding of TFIID to the
uninduced promoter may help heat-shock genes respond
more rapidly to an increase in temperature.
Cell type and differentiation-specific gene expression is
often regulated by the availability of specific transcription
factors. Genes that are expressed in specific organs contain
binding sites for cell type-specific transcription factors.
Thus, tissue-specific transcription is often regulated by
the precise arrangement of regulatory UAS motifs in the
promoter, the availability of the cognate transcription fac-
tors, and the way these transcription factors influence the
activity of the promoter. Thus, for example, the liver and
the brain encode for respectively liver- and brain-specific
transcription factors that ensure a tissue-specific expres-
sion gene expression. Since transcription factors are typ-
ically dimeric proteins, the exact composition of the two
FIGURE 5 Activation of transcription of heat-shock genes in partners may vary among cell types and have different
mammalian cells. The heat shock factor (HSF) is present as a
transcription regulatory properties.
monomer in normal cells. An increase in temperature results in
a trimerization of HSF, which binds to the heat shock element
(HSE). HSF is activated as a transcriptional enhancer protein by
phosphorylation. 3. Regulation of Transcription Elongation
Although transcription initiation has only been discussed,
RNA polymerase elongation is also an important step in
heat-shock proteins do not regulate other nuclear hormone regulating gene expression in eukaryotes. Thus, there are
receptors, such as the retinoic acid and thyroid hormone several examples where the RNA polymerase halts at spe-
receptors. Thus, these receptors bind DNA in the absence cific pause sites during elongation. To be able to com-
of the ligand. In this case ligand binding results in a con- plete the synthesis of the precursor-RNA the polymerase
formational change of the activation domain permitting has to be able to override this attenuation of transcrip-
binding of coactivator proteins. tion. The best-characterized example is the human im-
The second example concerns heat-shock activation of munodeficiency virus (HIV) Tat protein, which binds to a
transcription in mammalian cells (Fig. 5). When cells are stem-loop structure at the 5 end of the HIV transcript, the

subjected to an elevated temperature (heat shock) they re- TAR sequence. In the absence of the Tat protein, HIV tran-
spond by activating synthesis of a small number of genes scription terminates approximaqtely 50 nucleotides down-
encoding for so-called heat-shock proteins. These pro- stream of the initiation site. When Tat is present it binds
teins serve an important function during heat shock by to the TAR sequence and recruits a cyclin T/Cdk9 com-
binding to cellular proteins, which become denatured by plex which is responsible for phosphorylation of the CTD
the increase in temperature. Subsequently, the heat-shock tail of RNA polymerase II, thereby alleviating termina-
proteins help to renature the proteins to their native con- tion and permitting the RNA polymerase to synthesize the
formation. Transcription of heat-shock genes is controlled full-length HIV genomic RNA.
by the heat-shock transcription factor (HSF), which binds
to the heat-shock element (HSE) found in the promoter
of all genes regulated by heat shock. HSF is activated by IV. REGULATION OF TRANSCRIPTION
two mechanisms (Fig. 5). Thus, in normal cells HSF exists IN PROKARYOTES
as a monomer. An increase in temperature results in un-
folding of HSF, which exposes the DNA-binding domain
A. Introduction
and allows it to bind to other HSFs and form a trimer that
binds to the HSE. However, binding of HSF to DNA is The mechanisms to initiate transcription in eukaryotes and
not enough to activate transcription. Thus, HSF needs to prokaryotes are similar. As a comparison to control of
be modified by phosphorylation before it activates tran- transcription in eukaryotes some key features in transcrip-
scription of the heat-shock genes. Interestingly, TFIID is tional control in bacteria will be given. Prokaryotic cells
bound to the TATA element in heat-shock genes also in contain only one type of RNA polymerase, which is re-
uninduced cells. Thus, binding of an active HSF to the sponsibleforsynthesisofalltypesofRNA:mRNA,rRNA,