TFEC, A BASIC HELIX-LOOP-HELIX PROTEIN, FORMS HETERODIMERS WITH TFE3 AND INHIBITS TFE3-DEPENDENT TRANSCRIPTION ACTIVATION

We have identified a new basic helix-loop-helix (BHLH) DNA-binding pro tein, designated TFEC, which is closely related to TFE3 and TFEB. The basic domain of TFEC is identical to the basic DNA-binding domain of T FE3 and TFEB, whereas the helix-loop-helix motif of TFEC shows 88 and 85% identity with the same domains in TFE3 and TFEB, respectively. Lik e the other two proteins, TFEC contains a leucine zipper motif, which has a lower degree of sequence identity with homologous domains in TFE 3 and TFEB than does the BHLH segment. Little sequence identity exists outside these motifs. Unlike the two other proteins, TFEC does not co ntain an acidic domain, which for TFE3 mediates the ability to activat e transcription. Like the in vitro translation product of TFE3, the in vitro-translated TFEC binds to the muE3 DNA sequence of the immunoglo bulin heavy-chain gene enhancer. In addition, the product of cotransla tion of TFEC RNA and TFE3 RNA forms a heteromeric protein-DNA complex with muE3 DNA. In contrast to TFE3, TFEC is unable to transactivate a reporter gene linked to a promoter containing tandem copies of the imm unoglobulin muE3 enhancer motif. Cotransfection of TFEC DNA and TFE3 D NA strongly inhibits the transactivation caused by TFE3. TFEC RNA is f ound in many tissues of adult rats, but the relative concentrations of TFEC and TFE3 RNAs vary considerably in these different tissues. No T FEC RNA was detectable in several cell lines, including fibroblasts, m yoblasts, chondrosarcoma cells, and myeloma cells, indicating that TFE C is not ubiquitously expressed.