Revealing the Mechanism of HSP104 Transcription Initiation in the ...

In mammalian cells, Hsf1 is a monomeric cytoplasmic protein, that in
response to stress is recruited to the nucleus, trimerized and binds DNA (45, 90, 118,
133, 134). By contrast, in yeast, Hsf1 was shown to be constitutively homotrimerized
and to constitutively bind HSEs (61, 117). However, a more detailed study, that
analyzed Hsf1 binding in vivo using ChIP asays, suggested that some promoters bind
Hsf1 only following stress, similar to the case in mammalian cells (51, 135). It was
found that in Drosophila, upon activation, Hsf1 binds HSEs and recruits mediator
complexes to heat shock loci as part of a cascade of events leading to transcription
activation. In fact, this recruitment seems to involve direct interaction between Hsf1
and components of the mediator complex (95). In addition, Hsf1 of mammalian cells
has been shown to interact in vitro and in vivo with the chromatin remodeling
complex SWI/SNF (123). Chromatin remodeling activities on purified nucleosome
templates were also shown to be dependent upon their recruitment via Hsf1 (123).
These reports indeed lead to the finding that in yeast, interactions between Hsf1 and
components of the mediator do exist and that mediator complex can be recruited to
promoters via Hsf1 (39).
The STRE/Msn2/Msn4 system
As is shown in Figure 1, the promoter of HSP104 contains several repeats of
the sequence 5’ AGGGG 3’ or 5’ CCCCT 3’. These sequences are known as STress
Response Elements (STREs). STREs were originally identified in the promoters of
CTT1 and DDR2 genes [encoding the cytoplasmic catalase and DNA damage
response proteins respectively (68, 132)] whose transcription are highly induced
under oxidative stress and exposure to DNA damaging agents respectively.
Unexpectedly, it was found that CTT1 transcription was also elevated in response to
heat shock, although it does not contain any HSE (132). Furthermore, it has been
shown that DDR2 can be transcriptionally activated not only by DNA damaging
agents, but also by thirteen other stresses including osmotic shock, nitrogen starvation
oxidative stress and stationary phase (126). Promoter analysis of CTT1 and DDR2
revealed that transcription activation in response to all these stresses is dependent on
short sequences that were termed STREs (68, 86). STREs were then identified in the
promoters of hundreds of stress related genes (17, 91). The promoter of HSP104
contains three classical STREs positioned at -172, -220 and -252bp from the ATG
[Fig. 1 and ref. (47)].
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