MOLECULAR-CLONING OF CDNA-ENCODING A HUMAN TFEC ISOFORM, A NEWLY IDENTIFIED TRANSCRIPTIONAL REGULATOR

TFEC is a transcriptional repressor originally identified in rat chond rosarcoma and contains a basic helix-loop-helix and leucine zipper (bH LH/LZ) structure. TFEC shares a closely related bHLH/LZ structure with microphthalmia-associated transcription factor (MITF) and TFE3. In th e course of cDNA cloning for a factor structurally related to MITF whi ch is also a regulator for cell differentiation, we have isolated cDNA clones from a THP-1 human monocytic leukemia cell line. These cDNAs e ncode a protein of 347 amino acids, termed TFECL, a human homolog of a putative rat TFEC isoform. TFECL contains an acidic domain that corre sponds to a transcriptional activation domain of TFE3 but its equivale nt region is deleted in rat TFEC. We explored a function of TFECL usin g a melanocyte-specific tyrosinase gene and a ubiquitously expressed h eme oxygenase-l gene, each promoter containing the cis-acting CANNTG m otifs. By transient coexpression assays, we showed that TFECL is able to activate or inhibit transcription of a reporter gene linked to eith er the tyrosinase or the heme oxygenase-l gene promoter, depending on cell types. These results suggest that TFECL may function as a transcr iptional activator under certain conditions.