High mobility group protein 1 interacts specifically with the core domain of human TATA box-binding protein and interferes with transcription factor IIB within the pre-initiation complex

The high mobility group (HMG) box domain has defined a family of proteins, mostly transcription factors, that specifically interacts with DNA on the m inor groove and sharply bends it. The founding member of the family, HMG1, does not specifically recognize regular B-DNA but is recruited to DNA by in teraction with other transcription factors and TATA box-binding protein (TB P), However, conflicting effects of HMG1 on transcription have been reporte d. We show that the interaction between HMG1 and TBP is species specific. T his interaction in turn affects the interaction of TBP with transcription f actor (TF) LIE and is competed by TFIIA. A primary binding site was mapped to the H2' alpha-helix in the highly conserved core domain of human TBP. On HMG1, the primary binding site was only in the HMG box A, and HMG box A wa s also sufficient to interact with native TFIID. Both HMG boxes efficiently repressed transcription in vitro as fusions to the Gal4-DNA binding domain . Additionally, HMG box B showed a weak level of activation at very low amo unts. These results suggest a general involvement of HMG1 at the early stag es of polymerase II transcription that may result in subtle activation or r epression of individual genes.