The macrophage colony stimulating factor receptor encoded by the csf1r (formally known as c-fms) gene is a tyrosine kinase receptor which is essential for macrophage differentiation. This gene is upregulated during macrophage differentiation, but silenced in all non-macrophage cells. Previous studies have looked at the activation of csf1r within the myeloid lineage by investigating alterations in the ~hromatin structure of its cis-regulatory elements. However, the mechanism of repression is not fully understood.. ~My thesis examines the repression of csf1r in B cells. It was previously know that the trans~iption factor Pax5 is necessary forcsf1r repression. This thesis shows that Pax5 directly interacts with the csf1r promoter in a sequence specific manner and that the Pax5 deoxyribonucleic acid (DNA) binding domain alone is sufficient ~o repress csf1r. In addition, the recruitment of Pax5 does not lead to major alterations in the histone modification pr.ofile. This demonstrates tliat the mechanism of repression does not require the recruitment of chromatin modifying factors. The Pax5 binding site within the csf1r promoter overlaps with the region containing the major transcription start sites. This suggests that Pax5 represses csf1r by directly competing with the basal transcription machinery, rather than via epigenetic alterations of the chromatin. Besides the promoter, Pax5 interacts with the fms intronic regulatory element (FIRE). FIRE does not add a repressive activity to that of the csf1r promoter. Moreover, efforts to identify a Pax5 binding site on FIRE showed that Pc1lx5 does not directly bind to DNA, suggesting that the interaction was mediated by proteinprotein interactions. in vitro DNA-protein interaction studies were therefore carrried out, in this thesis and other studies, with nuclear extracts from myeloid cells and B cells to identify potential partners of Pax5. These experiments identified factors such as specificity protein 1 (Sp1), early growth factor 2 (Egr-2), PU.1, Runx 1 and CCAAT enhancer binding protein (C/EBP) bjnding to FIRE with both extracts, as well as several unidentified factors which could be potential interaction partners for Pax5. Antisense transcription start sites were identified in a previous study to be originating from FIRE. This thesis investigates the effect(s) of Pax5 on antisense promoter activity and clearly show that Pax5 is able to transactivate antisense promoter activity in B cells. Although the function of these antisense transcripts is currently unknown the elucidation of their regulation will potentially lead to the unveiling of their role during haematopoietic differentiation.