The packaging of DNA in the cell nucleus is a major obstacle, but also a crucial means of control in processes such as DNA replication, recombination and gene transcription. Studies in recent years have revealed that dynamic changes in the basic nucleosome structure of chromatin play a key role, particularly in the activation and silencing of gene expression. It is widely assumed that these changes are often linked to equally important, but as yet poorly understood, modifications of higher-order chromatin architecture. Recent studies in the fruit-fly Drosophila melanogaster show how protein complexes that bind to 'GAGA' DNA elements can replace nucleosomes to create a local chromatin environment that facilitates a variety of site-specific regulatory responses. In this article, I will summarize recent insights into the composition and architecture of GAGA-binding protein complexes, and discuss their multifaceted role in homeotic gene regulation.