During haematopoiesis, coordinated changes in transcription drive the differentiation of haematopoietic stem cells. Now Frank Grosveld and colleagues suggest that the LIM domain binding protein Ldb1 facilitates these transcriptional changes by forming distinct complexes with different partners(see p. 4913). Ldb1 is a cofactor for several DNA-binding proteins, including haematopoietic transcription factors. To find new Ldb1 binding partners, the researchers expressed biotin-tagged Ldb1 in C88 erythroleukaemic cells and pulled out interacting proteins with streptavidin-coated beads. New partners included the repressor protein Eto-2, the cyclin-dependent kinase Cdk9, and the bridging factor Lmo4. The researchers show that the composition of Ldb1 complexes changes during the differentiation of C88 cells. They also report that these Ldb1 partners are essential for definitive haematopoiesis in zebrafish and are coexpressed in pre-haematopoietic cells in mouse embryos. Finally, the researchers speculate that changes in Eto-2 and Lmo4 levels cause a shift from a large Ldb1-containing complex to a smaller complex that is required for haematopoiesis.