Self-assembly of DNA binding proteins can help control transcription initiation.

Transcription pioneer factors such as GAF (GAGA factor) are proteins essential for exposing DNA from highly packed eukaryotic chromatin. Experiments have recently shown that the assembly of GAF into higher-order oligomers is necessary for its pioneer function; however, they lack enough spatial or temporal resolution to study how oligomer formation impacts DNA transcription. Importantly, the distributions of GAFs and their targets on chromatin are non-homogeneous; thus, a spatial model is necessary. Here we implemented a rigid-body reaction-diffusion model to quantify how interactions between GAF proteins and between GAF to DNA control residence times, as measured by single-particle tracking experiments. We show how clusters of specific vs non-specific binding sites on the DNA can control the degree of oligomerization between the GAFs. Further, we can establish when stable oligomers can change the apparent affinity of GAF for the DNA binding sites. We characterize how 1D sliding along the DNA can promote oligomerization, even when nucleosomes can act as local barriers. With support from single-particle tracking data, our models show how mutations to specific binding domains shift the distributions of GAF throughout the nucleus. Our methods provide molecular mechanisms for how clustering between proteins can help them target specific DNA regions within the nucleus.