Conversion of Dorsal from an activator to a repressor by the global corepressor Groucho

Abstract

The Dorsal morphogen acts as both an activator and a repressor of transcription in the Drosophila embryo to regulate the expression of dorsal/ventral patterning genes. Circumstantial evidence has suggested that Dorsal is an intrinsic activator and that additional factors (corepressors) convert it into a repressor. These corepressors, however, have previously eluded definitive identification. We show here, via the analysis of embryos lacking the maternally encoded Groucho corepressor and via protein-binding assays, that recruitment of Groucho to the template by protein:protein interactions is required for the conversion of Dorsal from an activator to a repressor. Groucho is therefore a critical component of the dorsal/ventral patterning system.

Groucho proteins: transcriptional corepressors for specific subsets of DNA-binding transcription factors in vertebrates and invertebrates

“…The Drosophila Dorsal protein also has been shown to interact biochemically with Groucho and to exhibit Groucho-dependent repression in vivo (Dubnicoff et al 1997). Dorsal is a member of the NF-B/rel family of transcription factors (Fig.…”

“…Dorsal has been shown to function intrinsically as a transcriptional activator that binds to sites in the promoters of the ventral-specific genes to activate their transcription . Repression of the dorsal-specific genes requires the binding of Dorsal to sites within their promoters, and Groucho is also required for Dorsal-mediated repression of these promoters (Jiang et al 1992;Pan and Courey 1992;Courey and Huang 1995;Dubnicoff et al 1997). Because the interaction between Dorsal and Groucho is mediated by the rel domain that is found in NF-B and related mammalian transcription factors ( Fig.…”

“…Because the interaction between Dorsal and Groucho is mediated by the rel domain that is found in NF-B and related mammalian transcription factors ( Fig. 1; Dubnicoff et al 1997), it will be important to determine whether Groucho proteins can also interact with these mammalian proteins to similarly repress specific target genes.…”

“…First is the genetic requirement for Groucho for in vivo transcriptional repression by the various Drosophila partner proteins (Paroush et al 1994;Aronson et al 1997;Dubnicoff et al 1997;Jimenez et al 1997). Second is the observation that the Groucho proteins have intrinsic active transcriptional repressor activity when directly bound to target genes by fusion to a heterologous DNA binding protein (Fisher et al 1996).…”

“…The Groucho proteins serve as non-DNA binding corepressors for specific subsets of DNA-binding transcription factors, including the Hairy-related proteins, Runt domain proteins, Engrailed, and Dorsal, and they are essential for certain aspects of repression by each of these repressors (Paroush et al 1994;Fisher et al 1996;Aronson et al 1997;Dubnicoff et al 1997;Jimenez et al 1997). These family members have been shown to be widely expressed both during development and in the adult, in contrast to the more limited expression pattern of their DNA-binding partners (Hartley et al 1988;Stifani et al 1992;Miyasaka et al 1993;Schmidt and Sladek 1993;Choudhury et al 1997;Pflugrad et al 1997;Sharief et al 1997).…”