Scope of this thesis
For many years, the hematopoietic field has been a major topic of interest for many researchers. Despite this, sickle cell disease and ß-thalassemia are still the most common monogenetic disorders with approximately 300,000 new patients born ever year, and no low-threshold solutions have been developed in order to ban the impact of these diseases from the world. Recent progress indicates that we are coming closer to a permanent and satisfactory solution. It is well known that increased y-globin ameliorates the symptoms of ß-hemoglobinopathy patients. Genomewide association studies and linkage analysis have revealed transcription factors that were shown experimentally to be directly involved in hemoglobin switching. Since these transcription factors are poor targets for pharmacological intervention, the challenge is now to identify and functionally characterize the co-factors and epigenetic regulators interacting with these transcription factors.

In this thesis, I show the results of the analysis of new candidate y-globin modifiers, and their role during hematopoiesis in vivo.