The HMG proteins NHP6A/B assist in the binding of the TATA box
binding protein TBP to promoters.
Peter Eriksson, David J
Stillman
Dep. of Pathology, Univ of Utah, 30 North 1900 East, Salt
Lake City, UT 84132-2501, USA
The multifunctional architectural
transcription factor Nhp6 (from the redundant NHP6A and
NHP6B genes) is involved in the transcriptional activation by RNA
pol II and pol III. Nhp6 also functions in transcriptional elongation
with Spt16 and Pob3 in the SPN complex, related to mammalian FACT. Our
microarray data show that more than 300 genes are at least two fold
induced or repressed in a nhp6 mutant compared to wild-type. In
our research we now show that Nhp6 is important for the interaction of
the TATA box binding protein (TBP) with promoters. Overexpression of TBP
can suppress the Ts phenotype of a nhp6 mutant. This interaction
is supported by in vitro data implicating Nhp6 in stabilizing the
TBP-TFIIA-TFIIB preinitiation complex on DNA (Genes Dev 10:2769). We
have performed a genetic screen and identified a large number of TBP
point mutants that are synthetic lethal in a nhp6 mutant strain.
Many of these TBP mutations coincide with mutations that affect
formation of a bent DNA/TBP complex in a recent study showing that TBP
binds to DNA in a two step process (Cell 108:615). We propose a model
where Nhp6 assists the binding of TBP by pre-bending the DNA at the TATA
box. We will also present a number of genetic interactions between Nhp6
and other factors involved in transcriptional initiation, thereby
strengthening the link between Nhp6 and TBP.
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