CHIP, A WIDELY EXPRESSED CHROMOSOMAL PROTEIN REQUIRED FOR SEGMENTATION AND ACTIVITY OF A REMOTE WING MARGIN ENHANCER IN DROSOPHILA

The mechanisms allowing remote enhancers to regulate promoters several kilobase pairs away are unknown but are blocked by the Drosophila sup pressor of Hairy-wing protein (Suhw) that binds to gypsy retrovirus in sertions between enhancers and promoters. Suhw bound to a gypsy insert ion in the cut gene also appears to act interchromosomally to antagoni ze enhancer-promoter interactions on the homologous chromosome when ac tivity of the Chip gene is reduced. This implicates Chip in enhancer-p romoter communication. We cloned Chip and find that it encodes a homol og of the recently discovered mouse Nli/Ldb1/Clim-2 and Xenopus Xldb1 proteins that bind nuclear LIM domain proteins. Chip protein interacts with the LIM domains in the Apterous homeodomain protein, and Chip in teracts genetically with apterous, showing that these interactions are important for Apterous function in vivo. Importantly, Chip also appea rs to have broad functions beyond interactions with LIM domain protein s. Chip is present in all nuclei examined and at numerous sites along the salivary gland polytene chromosomes. Embryos without Chip activity lack segments and show abnormal gap and pair-rule gene expression, al though no LIM domain proteins are known to regulate segmentation. We c onclude that Chip is a ubiquitous chromosomal factor required for norm al expression of diverse genes at many stages of development. We sugge st that Chip cooperates with different LIM domain proteins and other f actors to structurally support remote enhancer-promoter interactions.