The DNA-binding factor TFE3 contains adjacent helix-loop-helix (HLH) and leucine zipper (LZ) domains flanked by an upstream basic region. These protein motifs are frequently observed in other transcription factors and are particularly common to members of the Myc family. TFE3 is ubiquitously expressed and can directly associates with DNA as either homodimers or heterodimers formed with two related proteins, TFEB or TFEC. TFE3 binds to and activates the microE3 motif of the immunoglobulin heavy-chain enhancer to induce B-cell-specific gene transcription and DNA recombination. TFEB binds to the major late promoter of adenovirus and specifically associates with DNA as both a homodimer and a heterodimer with TFE3. TFEB is expressed at low levels in the embryo but at high levels in the trophoblast cells of the placenta, where it plays a critical role in regulating normal vascularization of the placenta. TFEC shares a bHLH/LZ structure with TFE3 and a closely related protein microphthalmia-associated transcription factor (MITF), which is critically involved in melanocyte differentiation. Unlike TFE3, the expression of TFEC is largely restricted to fibroblasts, myoblasts, chondrosarcoma cells, and myeloma cells.