ChIP-seq in FLK1+ cells

The first hematopoietic and endothelial progenitors are derived from a common embryonic precursor termed the hemangioblast. At the molecular level, lineage choice and differentiation of multipotent cells to mature progeny are characterized by dynamic changes in gene transcription under the control of transcription factors (TFs). LDB1, TAL1 and GATA2 are hematopoietic TFs involved in hemangioblast development. Here we use a combination of ChIP-Sequencing, RNA-sequencing and bioinformatic analysis to understand their regulatory role at two different stages of hematopoietic development, BL-CFCs, the in vitro equivalent of the hemangioblast, versus hematopoietic pro-erythroblast progenitors cells. Our study shows that LDB1, TAL1 and GATA2 control a variety of different biological processes, acting mainly independently of one another. However there is also collaborative action between them as a protein complex and this specifically coordinates the expression of genes encoding key hematopoietic transcriptional regulators. During further development the low ratio of GATA over TAL1 increases to a high ratio during the so called GATA switch when the LDB1 complex binds many more gene regulatory sequences in addition to the key hematopoietic transcriptional regulators. Our study provides fundamental new insight into how combinatorial TF function controls a complex developmental process and we propose a model how the process of hematopoietic development is initiated.