TAF4 takes flight

Abstract

The eukaryotic mRNA transcription machinery is exceedingly complex, perhaps reflecting the requirement for response to diverse environmental and developmental signals. Some of the machinery is common to all mRNA genes and includes RNA polymerase II (Pol II) and a set of general transcription factors (GTFs) (1). Signal-specific gene expression patterns are defined by sequence-specific DNA-binding proteins (activators) that bind cognate sites in the promoter and enhancers of target genes. In most cases activators are not sufficient for stimulation of transcription. Instead, these DNA-binding proteins initiate the ordered assembly of large multiprotein complexes (the coactivators), in addition to the general factors, at the promoters of target genes (2). A cursory examination of the complexes involved in signal-responsive activated transcription in a chromatin environment indicates that >100 different polypeptides are involved in the process. Many of these proteins occur in stable multiprotein complexes. One of the central players in this process is TFIID. TFIID consists of the TATA-binding protein (TBP) and 12–13 TBP-associated factors (TAFs) (3). TFIID forms the heart of the preinitiation complex and DNA-binding proteins directly contact TFIID to stimulate the rate of transcription of target genes. An important remaining question in this field is to uncover how each individual polypeptide contributes to gene activation within the context of the entire complex. Experiments designed to test this are complicated because loss of one critical subunit of a complex often leads to disintegration of the entire complex (4–6). In a recent issue of PNAS, Wright and Tjian circumvent this problem and manage to dissect the role of a single TFIID subunit, TAF4 in … 1E-mail: mmarr{at}brandeis.edu