Local action of long-range repressors in the Drosophila embryo

• Published in: The EMBO journal Vol. 20; no. 9; pp. 2246 - 2253
• Main Authors: Nibu, Yutaka, Zhang, Hailan, Levine, Michael
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.05.2001; Blackwell Publishing Ltd; Oxford University Press
• Subjects: Alcohol Oxidoreductases; Amino Acid Motifs - physiology; Animals; Basic Helix-Loop-Helix Transcription Factors; Body Patterning - genetics; CtBP; dCtBP protein; Deoxyribonucleic acid; DNA; DNA - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drosophila; Drosophila Proteins; embryo; Embryo, Nonmammalian - metabolism; Embryos; Enhancer Elements, Genetic; Gene Silencing; Genes, Dominant; Groucho; Groucho protein; hairy gene; Insect Proteins - genetics; Krueppel protein; Kruppel-Like Transcription Factors; long-range repression; Models, Genetic; Phenotype; Phosphoproteins - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Regulatory Sequences, Nucleic Acid; Repressor Proteins - genetics; Repressor Proteins - metabolism; Snail Family Transcription Factors; Transcription Factors - genetics; Transgenes
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/20.9.2246

Previous studies have identified two corepressors in the early Drosophila embryo: Groucho and dCtBP. Both proteins are recruited to the DNA template by interacting with short peptide motifs conserved in a variety of sequence‐specific transcriptional repressors. Once bound to DNA, Groucho appears to mediate long‐range repression, while dCtBP directs short‐range repression. The short‐range Krüppel repressor was converted into a long‐range repressor by replacing the dCtBP interaction motif (PxDLSxH) with a Groucho motif (WRPW). The resulting chimeric repressor causes a different mutant phenotype from that of the native Krüppel protein when misexpressed in transgenic embryos. The different patterning activities can be explained on the basis of long‐range silencing within the hairy 5′ regulatory region. The analysis of a variety of synthetic transgenes provides evidence that Groucho‐dependent long‐range repressors do not always cause the dominant silencing of linked enhancers within a complex cis‐regulatory region. We suggest a ‘hot chromatin’ model, whereby repressors require activators to bind DNA.