Diploidy of Drosophila imaginal cells is maintained by a transcriptional repressor encoded by escargot.

Abstract

The Drosophila escargot (esg) gene encodes a C2-H2-type zinc finger protein that is expressed in the imaginal discs and histoblasts. In some esg mutants, the abdominal histoblasts become polyploid. It has therefore been suggested that the role of esg is to maintain diploidy of the imaginal cells. We show that esg encodes a DNA-binding protein with high affinity for G/ACAGGTG, the consensus-binding sequence for the basic helix-loop-helix (bHLH) family of transcription factors (E2 box). This DNA-binding activity is essential for esg function in vivo as the strong embryonic lethal allele esg TM is caused by an amino acid change within the zinc finger region, leading to reduced affinity for DNA. In cultured cells, a heterodimer of the bHLH proteins Scute and Daughterless activates transcription from promoters containing E2 boxes. The esg protein strongly inhibits this activation, suggesting that esg may regulate developmental processes dependent on bHLH proteins. In larvae, esg protein expressed by the heat shock promoter can rescue the polyploid phenotype of abdominal histoblasts, demonstrating that the phenotype is attributble to a loss of esg function, esg must be expressed continuously during the larval period for efficient rescue. Ectopic expression of esg in the salivary glands inhibits endoreplication of DNA. These results suggest that esg is involved in transcriptional inhibition of genes required for endoreplication.

Mouse Snail Family Transcription Repressors Regulate Chondrocyte, Extracellular Matrix, Type II Collagen, and Aggrecan

“…These results suggest that Snail and Slug suppress the activity through the promoter and not through the enhancer. Because of the significant similarity among the Snail family transcription repressors in the DNA binding domains, they are thought to regulate the same target genes (20). The identity of the last four zinc fingers between Snail and Slug is 82%.…”

Mammalian Scratch: A neural-specific Snail family transcriptional repressor

“…Because the Snail consensus binding sequence contains the E-box motif CAGGTG recognized by bHLH transcription factors (22) and functional interactions between Snail and bHLH proteins have been reported (13,23), we tested the ability of hASH1 to bind to the same sequence. When either hASH1 or E12, a heterodimerizing partner for bHLH proteins, was used alone, no or only a modest shift of the wild-type Snail probe was seen, respectively (data not shown).…”

Heterologous Expression of the Transcriptional Regulator Escargot Inhibits Megakaryocytic Endomitosis

“…In vitro binding site selection experiments using pools of random sequences have revealed that the consensus binding element corresponds to an E2 box that is recognized by a variety of basic helix-loop-helix transcriptional activators. It has been proposed that the Snail proteins may compete directly with basic helix-loop-helix proteins for the same binding sequences, although this has been observed only in a limited number of cases (19,20). Genetic studies in Drosophila, Xenopus, Caenorhabditis elegans, and mouse have shown that Snail proteins participate in a variety of processes that include mesoderm determination, neurogenesis, and apoptosis (13,14).…”

“…Further analysis revealed that Escargot is involved in the maintenance of diploidy in embryonic and larval cells (19). Thus, ectopic expression of escargot inhibits polyploidization in salivary glands, whereas its ablation prevents the regular progression through mitotic cycles in the imaginal tissues and, as a result, causes abdominal histoblasts to undergo endocycles and become polyploid (18,19).…”