Association of Ddx5/p68 protein with the upstream erythroid enhancer element (EHS1) of the Klf1 gene

EKLF/KLF1 is an essential transcription factor that plays a global role in erythroid transcriptional activation. Its own regulation is of interest, as it displays a highly restricted expression pattern, limited to erythroid cells and its progenitors. Here we use biochemical affinity purification to identify the Ddx5/p68 protein as an activator of KLF1 by virtue of its interaction with the erythroid-specific DNAse hypersensitive site upstream enhancer element (EHS1). We postulate that its range of interactions with other proteins known to interact with this element render it part of the enhanseosome complex critical for optimal expression of KLF1. These individual interactions provide quantitative contributions that, in sum, establish high level activity of the KLF1 promoter and suggest they can be selectively manipulated for clinical benefit.