LIM-homeodomain transcription factor (LIM-HD) regulated expression of genes that pattern the body and generate cell specificity during development in invertebrates and vertebrates. LIM-HD proteins are themselves regulated by both intramolecular and intermolecular interactions mediated by the LIM domains. LIM domains positively regulate LIM-HD activity by promoting protein-protein interactions that allow cooperative binding to regulatory regions of tissue-specific promoters. They also negatively regulate LIM-HD activity, possibly by preventing HD association with DNA. Interaction of LIM domains with other proteins relives this interference, permitting DNA binding and providing a mechanism for refining LIM-HD activity.