Transcriptional activators, and compositions and uses related thereto

DETAILED DESCRIPTION OF THE INVENTION I.
General Protein-encoding genes in eukaryotes are transcribed by RNA polymerase II (pol II), a multisubunit enzyme that is brought to an appropriate gene promoter (pol II promoter) through the assembly of a pre-initiation complex comprising a number of general transcription factors.
The multisubunit protein complex TFIID is required for transcription by most, if not all, promoters targeted by pol II.
Whereas the TATA-box binding protein (TBP) of TFIID is sufficient for basal transcription, pol II transcription is also regulated by gene-specific activator proteins.
Activator-dependent transcription requires, inter alia, TBP-associated proteins (TAFs) and other transcriptional cofactors.
One of the important concepts to emerge from studies of eukaryotic gene expression is that activators of pol II-dependent transcription are composed of functional modules whose abilities to bind to subunits of the ultimate pol II complexes regulates transcriptional activity of a nearby gene.
The present invention pertains to nucleic acid molecules and proteins which can be used to regulate the expression of genes in eukaryotic cells.
One aspect of the present invention relates to chimeric transcriptional activators ("composite activators") which are derived to include a multiplicity of heterologous "activation tags" (further defined infra), e.
g.
, polypeptide sequences capable of affecting transcriptional activation, as for example, affecting the assembly or stability of an active polymerase complex.
It has been discovered that activation tags from disparate proteins can be combined in a single polypeptide, or artificially recruited by a complex to a single recognition element and retain the ability to synergistically activate transcription.
In its simplest elaboration, the chimeric activator includes at least two different activation tags from heterologous sources, e.
g.
, activation tags which are derived from two or more different transcription factors or co-activators and which do not naturally occur together in the same protein