TEF, A TRANSCRIPTION FACTOR EXPRESSED SPECIFICALLY IN THE ANTERIOR-PITUITARY DURING EMBRYOGENESIS, DEFINES A NEW CLASS OF LEUCINE ZIPPER PROTEINS

We have identified and characterized a new member of the leucine zipper (bZIP) gene family of transcription factors, thyrotroph embryonic factor (TEF). Analysis of the ontogeny of TEF gene expression reveals the presence of TEF transcripts, beginning on embryonic day 14, only in the region of the rat anterior pituitary gland in which thyrotrophs arise. This pattern of gene expression corresponds temporally and spatially to the onset of thyroid-stimulating hormone (TSH-beta) gene expression, which defines the thyrotroph phenotype. Coupled with this observation, we find that TEF can bind to and trans-activate the TSH-beta promoter. In contrast to this restricted pattern of expression during embryogenesis, TEF transcripts appear in several tissues in the mature organism. We propose that TEF belongs to a new class of bZIP proteins on the basis of the unique homology between TEF and another member of the bZIP gene family, the albumin D box-binding protein (DBP). TEF and DBP transcripts are coexpressed in a pituitary cell line, and these two proteins can readily form heterodimers. The DNA-binding and dimerization domains of TEF correspond to those found in other bZIP proteins. We have however, identified a cluster of basic amino acids, found only in TEF and DBP, that is necessary for the proper DNA-binding site specificity of TEF. A major trans-activation domain of TEF resides outside the region of homology to other bZIP proteins. These data are consistent with a role for a member of a new class of bZIP transcription factors in activating gene expression in the developing thyrotroph.