FIG 8.

Extra- and intracellular inputs into regulation of EKLF/KLF1 expression. The BMP4 pathway is linked to erythroid hypersensitive site 1 (EHS1) via Smad5/Smad4, which also induces Gata1, leading to a coherent feed-forward activation loop. Although not shown in the model, Gata2 provides the initial impetus for EKLF and Gata1 expression. The “core” erythroid transcription network that includes Tal1, Ldb1, Gata1 or -2, and P300 is brought into play via the conserved Smad/Dek/Gata/E box/Gata layout at EHS1. Within the 49-bp EHS1 is the 18-bp oligo2 sequence that binds DEK and is important for the full integrity of the complex.