An ongoing question in evolutionary biology is how genes arising in new locations — through mobilization or de novo origination — establish appropriate expression patterns without disrupting the regulation of nearby, pre-existing genes. Such considerations are particularly pertinent in topologically associating domains (TADs) of chromosomes, as genes within the same TAD have shared repertoires of available regulatory elements, which might limit opportunities for distinct regulatory programmes. A new study in Cell describes how local chromatin features enable differential regulation of genes within TADs.