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

for their transcription, some 16% of the genes of S.cerevisiae do not need TAFs for
their transcription (59, 71, 113). However, the majority of TAFs are essential for
viability [reviewed in (48)], as are 10 of the twelve subunits of RNA PolII (23, 24).
Following binding of TFIID, more protein complexes are recruited to the promoter,
i.e., the TFIIB complex, which assists RNA PolII in selecting the transcription start
site. Then, the RNA PolII holoenzyme along with TFIIF, TFIIE, and TFIIH associate
with the promoter and form the PIC. Following establishment of PIC, promoter
melting and transcription initiation occur and are followed by hyperphoshorylation of
the C-terminal domain (CTD) of the RNA polymerase through the TFIIH kinase
activity. This leads to promoter clearance and elongation of transcription [reviewed
in (28)].
All of the above events do not occur automatically since inactive promoters
(such as promoters of heat shock genes in cells not exposed to stress) are not
accessible to TBP and the subsequent complexes. Such promoters are part of DNA
that is wrapped around histone proteins (two H2A-H2B heterodimers and a H3-H4
tetramer) which form nucleosomal structures. These nucleosomal structures are
further compacted into tightly super-coiled structures called chromatin. Therefore,
the binding of the basal transcription machinery and the formation of PIC are
hindered by these nucleosomes that have to be remodeled to enable transcription
initiation to occur. Thus, many preceding steps should take place in order to allow the
formation of PIC and transcription initiation. There is no general mechanism(s)
leading to chromatin remodeling and transcription initiation of all genes and each
promoter is activated in its own unique and specific way (2, 29, 42). Nevertheless, a
general mechanism leading to gene activation is believed to be the following. Upon
an activating signal there is binding of proteins known as transcriptional activators to
enhancer elements (also called upstream activating sequences) in the relevant
promoter and unbinding (where applicable) of transcriptional repressors. When
bound to enhancers, transcriptional activators recruit chromatin modifying complexes.
The main purpose of these chromatin modifications is to induce “melting” of
nucleosomal structures in order to reduce the histone-DNA interaction which enables
the assembly of PIC. Chromatin modifying complexes could be divided into two
general groups: i) Factors that, through the hydrolysis of ATP molecules, induce
conformational and spatial changes of nucleosomes (1, 43). ii) Factors that covalently
modify histones by either acetylation, phosphorylation, sumoylation, or methylation
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