Regulation of gene expression by transcription factor clustering

In developmental systems, like the fruit fly embryo, highly reproducible spatial patterns of gene expression are formed within minutes. This requires fast and precise interpretation of the nuclear concentrations of input transcription factors (TFs) by the regulatory sequence of the target genes. However, these factors, which are freely diffusing proteins in the nucleus, have previously been shown to be heterogeneously distributed. Here, we show that this apparent heterogeneity arises out of accumulation of the TFs into submicron clusters. Using several target genes of a prominent TF, we show that active gene loci coincide with these TF clusters. The physical properties of the clusters and their stability are highly dependent on the DNA regulatory sequences of these target genes, but not on the nuclear concentration of the TF proteins. These results suggest that such cluster formation might confer robustness against input signal fluctuations.