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

HSP104 mRNA in different mutants show, indeed, the robustness of HSP104
transcription that is rarely affected by the absence of activators and other transcription
factors.
Through monitoring the acetylation states of histones, we suggest that
induction of HSP104 transcription requires that acetylated H3 and H4 molecules be
absent. We observed that under optimal growth conditions all H4 histones on the
HSP104 promoter are acetylated as well as major fractions of H3 histones. Under
these conditions, only in ras2∆ cells, concentrations of acetylated H3 and H4 are
lower and the promoter is even occupied with non-acetylated H4. As in this strain the
HSP104 promoter is constitutively active, there is clear correlation between promoter
activity and non-acetylated histones. Current dogma of gene activation claims that
acetylation of histones followed by the dissociation of nucleosomes from promoters is
required for promoter activation (28, 49, 50). The case for HSP104 is different.
There is no global dissociation of histones from the promoter, but rather a specific
dissociation of acetylated H3 molecules from nucleosomal structures and
deacetylation of H4 molecules. Non-acetylated H3 proteins remain associated with
nucleosomes even in response to heat shock and so do histone H4 molecules that are
now not acetylated. Although not very common, the disassembly and deacetylation
patterns we observe for HSP104 in response to heat shock should not be that
surprising. As described in Deckert et al (31) histone deacetylation can also lead to
transcription initiation of several stress-responsive genes. Also, a recent study also
demonstrated that some promoters, namely GAL induced promoters, are activated by
histone deacetylation (31).
However, our conclusion differs somewhat from that of Deckert and Struhl
(31). These investigators also monitored a dramatic decrease in acetylated histones
on the HSP104 promoter in response to heat shock [18 fold decrease of acetylated H4
and 10 fold decrease in acetylated H3 (31)]. Yet, as there was some decrease in the
level of unacetylated H4 occupancy (30%) they concluded that there is altogether
chromatin remodeling or disassembly of the nucleosomes. We suggest that the
changes on the chromatin should not be taken as all-or-non activity (disassembly, or
deacetylation). There seems to be a series of different events which we partly
revealed; i.e., histones H4 are deacetylated, and acetylated H3 molecules are
disassembled from nucleosomes. Also, these changes are transient and reflect the
dynamic nature of the changes occurring on the promoter during continuous exposure
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