Fig. 9.

Proposed interaction among multiple transcription factors in the 260 bp upstream region of the human DBH gene.A, In DBH-positive cells, transcription factors interacting with domains I–IV, including cell type specific factors (e.g., Phox2a, Phox2b, and AP2) and general transcription factors (e.g., CREB and Sp1), synergistically activate the DBH transcription (+++). B, When any of these domains, domain II motif in this example, is mutated, the synergism is disrupted and robust transcription cannot occur (+/−) although DNA–protein interactions at the other sites are intact (Fig. 2). C,D, In DBH-negative cells, cell-specific Phox2a/Phox2b and AP2 are absent or present in lower amount compared with DBH-positive cells, respectively. Accordingly, synergistic activation of DBH gene transcription cannot occur whether or not domain II is intact (+/−).