Multiple related c&active elements required for cellspecific activation of the rat prolactin gene appear to bind a pituitary-specific positive transcription factor (s), referred to as Pit-l. DNA complementary to Pit-l mRNA, cloned on the basis of specific binding to AT-rich cell-specific elements in the rat prolactin and growth hormone genes, encodes a 33 kd protein with significant similarity at its carboxyl terminus to the homeodomains encoded by Drosophila developmental genes. Pit-l mRNA is expressed exclusively in the anterior pituitary gland in both somatotroph and lactotroph cell types, which produce growth hormone and prolactin, respectively. Pit-l expression in heterologous cells (HeLa) selectively activates prolactin and growth hormone fusion gene expression, suggesting that Pit-l is sufficient to confer a characteristic pituitary phenotype. The structure of Pit-l and its recognition elements suggests that metazoan tissue phenotype is controlled by a family of transcription factors that bind to related c&-active elements and contain several highly conserved domains. introduction

The precise temporal and spatial patterns of development are controlled by sequential activation of a hierarchy of regulatory genes (Gehring, 1987; Scott and Carroll, 1987). Utimately, organ identity is dictated by specific patterns of gene expression. In mammals, indirect evidence supports the existence of tissue-specific factors critical for the transcriptional activation of the genes that define cellular phenotype (eg, Walker et al., 1983; Staudt et al., 1986; Nelson et al., 1986; Bodner and Karin, 1987; Hammer et al., 1987a, 1987b; Courtois et al., 1987; Costa et al., 1988; Nelson et al., 1988; Singh et al., 1988). The development of the anterior pituitary gland provides an excellent model system in which to study cellspecific gene activation. Pituitary development results in five distinct cell types derived from a common lineage that are distinguished on the basis of the secreted hormone.