Krüppel-like-factor 1 (KLF1) is a developmentally regulated transcription factor expressed uniquely within the red blood cell lineage in both mouse and humans. A member of the C2H2 zinc finger transcription factor family, KLF1 has been shown to bind to the promoters and/or enhancers of many genes critical to erythropoiesis and activate their expression.

Pioneer factors are a class of transcription factors that are able to interact with ‘closed’ DNA that is wound around nucleosomes. They ‘pioneer’ the way for other factors to bind by re-positioning nucleosomes, exposing the hitherto occluded DNA. The relative permissiveness of DNA loci can be measured using ATAC-seq (Assay for Transposase-Accessible Chromatin) which relies on the DNA being accessible (i.e. nucleosome free) to a Tn5 transposase loaded with next-generation sequencing adaptors.

Here, using a tamoxifen inducible version of mouse KLF1 (Gillinder et al., 2016) we demonstrate that the KLF1 protein possesses pioneering transcription factor activity. Upon induction we find that KLF1 is translocated to the nucleus and at 3 hours occupies ~3800 genomic regions. Of these the majority show an increase in chromatin accessibility over the parental KLF1 null cell line, although many of the KLF1 bound sites are already ‘open’ prior to KLF1 induction.

Many of these sites are in well-known erythroid enhancers and super-enhancers such as the alpha-globin locus control region (Hay et al., 2016). We are undertaking ChIP-seq experiments to determine whether KLF1 recruits mediator and/or other ‘settler’ transcription factors. KLF4 is known to act as a pioneer factor in iPS cell generation, so we suggest many or even most members of the KLF family may function as pioneers in genome re-programming and development.