DTEF-1, A NOVEL MEMBER OF THE TRANSCRIPTION ENHANCER FACTOR-I (TEF-1)MULTIGENE FAMILY

M-CAT motifs mediate muscle-specific transcriptional activity via inte raction with binding factors that are antigenically and biochemically related to vertebrate transcription enhancer factor-1 (TEF-1), a membe r of the TEA/ATTS domain family of transcription factors. M-CAT bindin g activities present in cardiac and skeletal muscle tissues cannot be fully accounted for by existing cloned isoforms of TEF-1. TEF-1-relate d cDNAs isolated from heart libraries indicate that at least three cla sses of TEF-1-related cDNAs are expressed in these and other tissues. One class are homologues of the human TEF-1 originally cloned from HeL a cells (Xiao, J. H., Davidson, I., Matthes, H., Garnier, J. M., and C hambon, P. (1991) Cell 65, 551-568). A second class represents homolog ues of the avian TEF-1-related gene previously isolated (Stewart, A. F ., Larkin, S. B., Farrance, I. K., Mar, J. H., Hall, D. E., and Ordahl , C. P. (1994) J. Biol. Chem. 269, 3147-3150). The third class consist s of a novel, divergent TEF-1 cDNA, named DTEF-1, and its preliminary characterization is described here. Two isoforms of DTEF-1 (DTEF-1A an d DTEF-1B) were isolated as 1.9-kilobase pair clones with putative ope n reading frames of 433 and 432 amino acids whose differences are attr ibutable to alternative splicing at the C terminus of the TEA DNA bind ing domain. Cardiac muscle contains high levels of DTEF-1 transcripts, but unexpectedly low levels are detected in skeletal muscle, DTEF-1 t ranscripts are present at intermediate levels in gizzard and lung, and at low levels in kidney. DTEF-1A is a sequence-specific M-CAT-binding factor. The distinct spatial pattern of expression, and unusual amino acid sequence in its DNA binding domain, may indicate a particular ro le for DTEF-1 in cell-specific gene regulation. Recent work also sugge sts that at least one more TEF-1-related gene exists in vertebrates. W e propose a naming system for the four TEF-1 gene family members ident ified to date that preserves existing nomenclature and provides a mean s for extending that nomenclature as additional family members may be identified.