In multicellular organisms, genes are turned on and off in robust spatial and temporal patterns. Regulatory elements that activate or silence gene transcription are inherently promiscuous and can act over long genomic distances. A basic question is how regulatory elements find their target promoters and restrict their activity to their targets. By studying how specific gene expression patterns arise in developing Drosophila, our lab demonstrated that structural proteins form physical boundaries in the fly genome and critically prevent regulatory crosstalk. We also uncovered that structural proteins form chromosomal “loops” essential for activating specific neuronal genes over millions of base pairs, representing the longest-range regulatory associations ever reported in any genome.