In the presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related 
chemicals, the Ah receptor nuclear translocator (Arnt) forms a heterodimeric 
complex with the ligand-bound Ah receptor, leading to recognition of 
dioxin-responsive elements within the enhancer of the CYP1A1 gene and 
transcription activation by an unknown mechanism. To understand the role of Arnt 
in transcription activation by the Ah receptor-Arnt heterodimer, we performed a 
deletion analysis of Arnt to locate domains that are directly involved in 
transcription activation. We showed that the C-terminal 34 amino acids of Arnt 
encode a transcription activation domain (TAD) that functions independently of 
other sequences in the Ah receptor complex when attached to the heterologous 
Gal4 DNA binding domain. Deletion of the C-terminal acidic-rich 14 amino acids 
completely abolishes activity. Sequences important in Arnt TAD function were 
independent of the glutamine-rich region which is an important structural 
feature in the TAD of other transcription factors. The strength of the Arnt TAD 
when compared with the strong TAD from the herpes simplex virus VP16 protein was 
cell-type specific. Both the Arnt and VP16 TAD were equally strong in COS-1 
cells, but the Arnt TAD had weak activity in an Arnt-deficient mouse hepatoma 
cell line and was not needed for restoration of CYP1A1 activation. These results 
imply that for CYP1A1 activation the Ah receptor provides the dominant 
activation function for the heterodimer in hepatoma cells. The potential of the 
Arnt TAD to contribute to activation by the Ah receptor complex is likely 
determined by availability or activity of cell-specific factors with which the 
TAD interacts.