A. Barberis et L. Gaudreau, Recruitment of the RNA polymerase II holoenzyme and its implications in gene regulation, BIOL CHEM, 379(12), 1998, pp. 1397-1405
In yeast cells, interaction between a DNA-bound protein and a single compon
ent of the RNA polymerase II (poIII) holoenzyme is sufficient to recruit th
e latter to a promoter and thereby activate gene transcription. Here we rev
iew results which have suggested such a simple mechanism for how genes can
be turned on. The series of experiments which eventually led to this model
was originally instigated by studying gene expression in a yeast strain whi
ch carries a point mutation in Gal11, a component of the poIII holoenzyme.
In cells containing this mutant protein termed Gal11P, a derivative of the
transcriptional activator Gal4 devoid of any classical activating region is
turned into a strong activator. This activating function acquired by an ot
herwise silent DNA-binding protein is solely due to a novel and fortuitous
interaction between Gal11P and a fragment of the Ga14 dimerization region g
enerated by the P mutation. The simplest explanation for these results is t
hat tethering Gal11 to DNA recruits the poIII holoenzyme and, consequently,
activates gene transcription. Transcription factors that are believed not
to be integral part of the poIII holoenzyme but are nevertheless required f
or this instance of gene activation, e.g, the TATA-binding TFIID complex, m
ay bind DNA cooperatively with the holoenzyme when recruited to a promoter,
thus forming a complete poIII preinitiation complex. One prediction of thi
s model is that recruitment of the entire poIII transcription complex and c
onsequent gene activation can be achieved by tethering different components
to DNA. Indeed, fusion of a DNA-binding domain to a variety of poIII holoe
nzyme components and TFIID subunits leads to activation of genes bearing th
e recognition site for the DNA-binding protein. These results imply that ac
cessory factors, which are required to remove or modify nucleosomes do not
need to be directly contacted by activators, but can rather be engaged in t
he activation process when the poIII complex is recruited to DNA. In fact,
recruitment of the poIII holoenzyme suffices to remodel nucleosomes at the
PHO5 promoter and presumably at many other promoters. Other events in the p
rocess of gene expression following recruitment of the transcription comple
x, e.g. initiation, promoter clearance, elongation and termination, could u
nravel as a consequence of the recruitment step and the formation of an act
ive preinitiation complex on DNA. This view does not exclude the possibilit
y that classical activators also act directly on chromatin remodeling and p
ost-recruitment steps to regulate gene expression.