Hematopoiesis is the process responsible for the production of the many different blood cell types in our circulation. It is an ongoing process throughout life designed for the continuous replenishment of the different blood cells from a small population of self-renewing, pluripotential hematopoietic stem cells (HSCs). HSCs commit and differentiate along specific lineages in response to specific signals and according to the action of lineage-restricted transcription factors, which serve to execute lineage decision, commitment and differentiation programs through the concerted regulation of target genes. The functional association of specific transcription factors with the differentiation of particular hematopoietic lineages has been revealed from gene knockout experiments, however, little is known about the molecular basis of their functions in directing hematopoietic development and differentiation. For example, whilst there is mounting evidence that transcription factors have dual roles as activators and repressors, little is known as to how they exert these seemingly opposite functions at the level of chromatin structure.

Our research aims to address the molecular basis of transcription factor function by focusing on specific transcription factors involved in the differentiation of the erythroid (red blood) lineage, such as GATA-1. We are employing an in vivo biotinylation tagging approach as an efficient, high affinity method for the rapid isolation and characterization by mass spectrometry of transcription factor complexes implicated in erythroid differentiation and for the elucidation of gene target networks regulated by these complexes.

Our research group coordinate the FP7 Marie Curie Initial Training Network InteGeR aimed at an integrated approach to studying gene regulation in cellular differentiation, thus contributing to a better understanding of physiological and disease mechanisms.