Chip, a widely expressed chromosomal protein required for segmentation and activity of a remote wing margin enhancer in Drosophila

Abstract

The mechanisms allowing remote enhancers to regulate promoters several kilobase pairs away are unknown but are blocked by the Drosophila suppressor of Hairy-wing protein (Suhw) that binds to gypsy retrovirus insertions between enhancers and promoters. Suhw bound to a gypsy insertion in the cut gene also appears to act interchromosomally to antagonize enhancer-promoter interactions on the homologous chromosome when activity of the Chip gene is reduced. Development of multicellular organisms requires precise temporal and spatial regulation of gene expression. Much of this regulation depends on proteins that bind transcription enhancers. For enhancers separated by a few hundred base pairs from their promoter, DNA looping may be sufficient to allow interactions between basal factors at the promoter and the enhancer-binding proteins. Many complex developmentally regulated genes, however, contain multiple enhancers, which can be many kilobase pairs from the promoter. Enhancers require more than DNA looping to interact with the promoter over such remote distances. For instance, either a UAS or a higher eukaryotic enhancer must be upstream and promoter-proximal to activate transcription in yeast cells, yet both will function downstream of the gene in higher eukaryotic cells (Struhl 1989). This suggests that, in contrast to yeast, higher eukaryotes have factors that facilitate remote enhancer-promoter interactions.The effects of insertions of the gypsy retrovirus on enhancer activity in Drosophila lend support to the enhancer-facilitator hypothesis. Gypsy insertions block enhancer-promoter communication, without inactivating either the enhancer or promoter, when, and only when, they are between the enhancer and promoter (for review, see Dorsett 1996; Geyer 1997). The Suhw protein encoded by suppressor of Hairy-wing [su(Hw)] that binds to specific sequences in gypsy insertions is necessary and sufficient to block enhancers.A common domain in Suhw is required for gypsy insertions to block enhancers in several different genes (Harrison et al. 1993;Kim et al. 1996), suggesting that Suhw blocks all enhancers by the same mechanism. Enhancer blocking is distance independent and reversible (Dorsett 1993), and blocked enhancers remain active because they can activate a second promoter in the other direction (Cai and Levine 1995;Scott and Geyer 1995

The LIM-only protein, LMO4, and the LIM domain-binding protein, LDB1, expression in squamous cell carcinomas of the oral cavity

“…The LIM domain of LDBs contributes to the binding of transcription factors, including LIM-homeodomain, zinc-finger and basic helixloop -helix (bHLH) proteins (Agulnick et al, 1996;Jurata et al, 1996;Bach et al, 1997;Morcillo et al, 1997). Formation of protein complexes synergistically activates the expression of target genes Milán et al, 1998).…”

Insulators are fundamental components of the eukaryotic genomes

“…Thus, an alternative model involving proteins named facilitators that bring the enhancer and the promoter close to each other can be considered. Among these facilitators, the Drosophila Chip protein has been found to interact with Su(Hw) (Morcillo et al, 1997). Genetic evidence has shown that Su(Hw) becomes a more effective insulator when enhancerpromoter communication is weakened by mutations in Chip.…”

Dynamic spatiotemporal expression of LIM genes and cofactors in the embryonic and postnatal cerebral cortex

“…The data suggest the possibility of either novel LIM-HD proteins expressed in Clim1a-positive cell groups or, alternatively, a LIM-HD-independent role for Clim1a in these cells. Support for the latter scenario comes from studies on Drosophila segmentation, where CHIP, the Drosophila homolog of Clim2, appears to have broad functions beyond interacting with LIM proteins (Morcillo et al, 1997). CHIP is required for embryonic segmentation, and interacts with diverse homeodomain proteins by means of residues distinct from those that interact with LIM domains (Torigoi et al, 2000).…”