The genome is fantastically organised within the nuclear space. In situ HiC, one of the latest iterations of chromatin conformation capture techniques, allows genome-wide determination of this three-dimensional organisation across a cell population. Using in situ HiC and diffHic, our novel bioinformatics package designed to identify changes in organisation, we have shown that immune cell populations display distinct genome architecture. While population-specific genome organisation is an important finding it itself, it also raises an important question: how is such distinct architecture established and maintained? We went on to show that the deletion of a key lineage-defining transcription factor dramatically reduces organisation of the genome in immune cell progenitors. Importantly, this loss of organisation is enriched in DNA structures that are physically associated with the transcription factor, suggesting a direct role for the transcription factor in maintaining organisation. Furthermore, inducible reintroduction of this factor drives re-establishment of much of the genome organisation over just 24 hours. Thus, in addition to their canonical role of directly regulating gene expression, it appears that transcription factors also establish and maintain global genome organisation within immune cells.