Proteins organise the genome across multiple length and time scales. How proteins collectively bridge these scales to generate structure execute enzymatic reactions remains an open question. In this talk, I will discuss our work on dissecting biophysical mechanisms of genome self-organization, and how these principles are linked to transcription. To tackle these questions, we use interdisciplinary approaches that combine single molecule biophysics, reconstitution biology, and theory. I will describe how protein condensation acts as an organizing principle of genome organization, generating forces on DNA that then act as active enzymatic scaffolds.