Cloning and characterization of the murine genes for bHLH-ZIP transcription factors TFEC and TFEB reveal a common gene organization for all MiT subfamily members

The microphthalmia-TFE (MiT) subfamily of basic helix-loop-helix leucine zi pper (bHLH-ZIP) transcription factors, including TFE3, TFEB, TFEC, and Mitf , has been implicated in the regulation of tissue-specific gene expression in several cell lineages. In this report, we investigate the genomic organi zation and structural relatedness of MiT transcription factors. We characte rized the gene for mTFEC, which covers a region of more than 50 kb and is c omposed of seven exons. Further, we cloned a cDNA for the murine TFEE homol ogue and characterized its genomic structure. The eight coding exons of mTF EB are distributed over a 6-kb region. A multiple alignment of amino acid s equences of known MiT subfamily members indicates undescribed, conserved N- terminal regions and common putative phosphorylation sites for TFE3, TFEE, and Mitf. Also, intron-exon borders for characterized MiT genes appear comp letely conserved. A new family member and closely related putative transcri ption factor in Caenorhabditis elegans was identified by database searches that show a similar genomic organization within the bHLH-ZIP region and the acidic domain. Evolutionary aspects and implications for structure-functio n relationships are discussed. (C) 1999 Academic Press.