The transcription factor GATA1 regulates multiple genes in erythroid lineage cells. However, the means by which GATA1 regulates the expression of target genes during erythropoiesis remains to be elucidated. Three mechanisms have been postulated for the regulation of genes by GATA1. First, individual target genes may have multiple discrete thresholds for cellular GATA1. GATA1 has a dynamic expression profile during erythropoiesis, thus the expression of a set of GATA1 target genes may be triggered at a given stage of differentiation by cellular GATA1. Second, the expression of GATA1 target genes may be modified, at least in part, by GATA2 occupying the GATA-binding motifs. GATA2 is expressed earlier in erythropoiesis than GATA1, and prior GATA2 binding may afford GATA1 access to GATA motifs through epigenetic remodeling and thus facilitate target gene expression. Third, other regulatory molecules specific to each target gene may function cooperatively with GATA1. If GATA1 is required for the expression of such cofactors, a regulatory network will be formed and relevant gene expression will be delayed. We propose that the stage-specific regulation of erythroid genes by GATA1 is tightly controlled through a combination of these mechanisms in vivo.