Core Promoter Binding by Histone-Like TAF Complexes

14 TBP-associated factors (TAFs). Most of them contain a histone fold domain (HFD) that lacks the DNA-contacting residues of histones. Whether and how TAF HFDs contribute to core promoter DNA binding are yet unresolved. Here we examined the DNA binding activity of TAF9, TAF6, TAF4b, and TAF12, which are related to histones H3, H4, H2A, and H2B, respectively. Each of these TAFs has intrinsic DNA binding activity adjacent to or within the HFD. The DNA binding domains were mapped to evolutionarily conserved and essential regions. Remarkably, HFD-mediated interaction enhanced the DNA binding activity of each of the TAF6-TAF9 and TAF4b-TAF12 pairs and of a histone-like octamer complex composed of the four TAFs. Furthermore, HFD-mediated interaction stimulated sequence-specific binding by TAF6 and TAF9. These results suggest that TAF HFDs merge with other conserved domains for efficient and specific core promoter binding. Transcription of protein-encoding genes in eukaryotes in-volves the assembly of RNA polymerase II and general tran-scription factors (GTFs) on the core promoter to form a preinitiation complex (PIC). TFIID is the major DNA-binding GTF. It is composed of the TATA-binding protein (TBP) and 14 TBP-associated factors (TAFs). TAFs regulate transcrip-tion at multiple levels. Certain TAFs interact with activators to facilitate PIC formation (2, 18) and transcription reinitiation (1). TAFs also have a role in recognition and binding to core promoter elements. DNase I footprinting revealed direct con-tact of TAFs with sequences upstream and downstream of th