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 zipper (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 organization and structural relatedness of MiT transcription factors. We characterized the gene for mTFEC, which covers a region of more than 50 kb and is composed of seven exons. Further, we cloned a cDNA for the murine TFEB homologue and characterized its genomic structure. The eight coding exons of mTFEB are distributed over a 6-kb region. A multiple alignment of amino acid sequences of known MiT subfamily members indicates undescribed, conserved N-terminal regions and common putative phosphorylation sites for TFE3, TFEB, and Mitf. Also, intron-exon borders for characterized MiT genes appear completely conserved. A new family member and closely related putative transcription 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-function relationships are discussed.
Rehli
M
M
Department of Biochemistry, University of Queensland, Brisbane, Queensland, Q4072, Australia.
Den Elzen
N
N
Cassady
A I
AI
Ostrowski
M C
MC
Hume
D A
DA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D017173:Caenorhabditis elegans / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D020161:Physical Chromosome Mapping; D015183:Restriction Mapping; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C069203:TFE3 protein, human; C082272:TFEC protein, human; C484068:Tcfeb protein, mouse; C484069:Tcfec protein, mouse; D014157:Transcription Factors; C068486:Tcfe3 protein, mouse