CONTEXT-DEPENDENT TRANSACTIVATION DOMAINS ACTIVATE THE IMMUNOGLOBULIN-MU HEAVY-CHAIN GENE ENHANCER

Enhancers and promoters nucleate the assembly of multiprotein complexe s that are required for the transcriptional activation of eukaryotic g enes. Although multimerized binding sites of individual transcription factors sometimes mimic the properties of an enhancer, the combinatori al use of factors is considered to be crucial for achieving biological specificity. The minimal B cell specific immunoglobulin mu heavy chai n gene enhancer is activated by a combination of tissue-restricted ETS proteins and ubiquitously expressed basic helix-loop-helix transcript ion factors. Here we show that a domain of PU.1 that activates transcr iption from multimerized PU.1 binding sites is not required to activat e the mu enhancer together with Ets-1. In contrast, a transactivation domain in Ets-1 is necessary to activate this enhancer synergistically with PU.1. Furthermore, the Ets-1 activation domain functions only wh en tethered to the mu A site of the enhancer. These observations illum inate two forms of context dependence: first, all possible transcripti on activation domains may not be required to achieve combinatorial spe cificity; second, functional transcription activation domains may requ ire appropriate positioning on DNA.