ESTROGEN-INDUCED APOPTOSIS BY INHIBITION OF THE ERYTHROID TRANSCRIPTION FACTOR GATA-1

Steroid hormones regulate diverse biological functions, including prog rammed cell death (apoptosis). Although steroid receptors have been st udied extensively, relatively little is known regarding the cellular t argets through which apoptosis is triggered, We show here that the lig and-activated estrogen receptor (ER) induces apoptosis in an erythroid cell line by binding to, and consequently inhibiting the activity of, GATA-1, an erythroid transcription factor essential for the survival and maturation of erythroid precursor cells, GATA-1 inhibition is refl ected in the downregulation of presumptive GATA-1 target genes, Consti tutive overexpression of a GATA-binding protein resistant to the effec ts of the ER partially rescues ER-induced apoptosis, Induction of apop tosis by a mutant ER defective in binding to the estrogen response ele ment but active in GATA-1 inhibition suggests that ER-mediated inhibit ion of GATA-1 is direct and does not require estrogen response element -dependent transcriptional activation, Thus, a lineage-restricted tran scription factor, such as GATA-1, constitutes one cellular target thro ugh which steroid hormones may control apoptosis, As GATA-binding prot eins are evolutionarily conserved, we speculate that members of the st eroid receptor family may exert some of their diverse biological funct ions in different cellular contexts through interference with the func tion of GATA-binding proteins.