SELECTIVE UTILIZATION OF BASIC HELIX-LOOP-HELIX-LEUCINE ZIPPER PROTEINS AT THE IMMUNOGLOBULIN HEAVY-CHAIN ENHANCER

The mu E3 E box within the immunoglobulin heavy-chain (IgH) enhancer b inds several proteins of the basic helix-loop-helix-leucine zipper (bH LHzip) class, including TFE3, USF1, and Max, Both TFE3 and USF have be en described as transcriptional activators, and so we investigated the ir possible roles in activating the IgH enhancer in vivo, Although TFE 3 activated various enhancer-based reporters, both USF1 and Max effect ively inhibited transcription, Inhibition by USF correlated with the l ack of a strong activation domain and was the result of the protein ne utralizing the mu E3 site, The effects of dominant-negative derivative s of TFE3 and USF1 confirmed that TFE3, or a TFE3-like protein, is the primary cellular bHLHzip protein that activates the IgH enhancer, Tn addition to providing a physiological role for TFE3, our results call into question the traditional view of USF1 as an obligate transcriptio nal activator.