Abstract
The Drosophila gene groucho (gro) encodes a transcriptional corepressor that has critical roles in many development processes. In an effort to illuminate the mechanism of Gro-mediated repression, we have employed Gro as an affinity reagent to purify Gro-binding proteins from embryonic nuclear extracts. One of these proteins was found to be the histone deacetylase Rpd3. Protein-protein interaction assays suggest that Gro and Rpd3 form a complex in vivo and that they interact directly via the glycine/proline rich (GP) domain in Gro. Cell culture assays demonstrate that Rpd3 potentiates repression by the GP domain. Furthermore, experiments employing a histone deacetylase inhibitor, as well as a catalytically inactive form of Rpd3, imply that histone deacetylase activity is required for efficient Gro-mediated repression. Finally, mutations in gro and rpd3 have synergistic effects on embryonic lethality and pattern formation. These findings support the view that Gro mediates repression, at least in part, by the direct recruitment of the histone deacetylase Rpd3 to the template, where it can modulate local chromatin structure. They also provide evidence for a specific role of Rpd3 in early development.
Highlights
The Drosophila gene groucho encodes a transcriptional corepressor with many roles in development
A peptide recovered from p68 has the sequence YGEYFPGTGDLR, which perfectly matches a sequence found in Drosophila histone deacetylase Rpd3 (De Rubertis et al 1996)
Rpd3 form a complex in vivo, that they interact via the glycine/proline rich (GP)-rich domain in Gro, and that this interaction contributes to transcriptional repression
Summary
The Drosophila gene groucho (gro) encodes a transcriptional corepressor with many roles in development (for reviews, see Fisher and Caudy 1998; Parkhurst 1998) This factor contains a conserved WD repeat domain implicated in protein–protein interactions but lacks a DNA-binding domain. Hairy-related basic helix– loop–helix (bHLH) factors, as well as Runt family transcription factors negatively regulate genes controlling neurogenesis, segmentation, and sex-determination via a conserved carboxy-terminal WRPW or WRPY motif through which they recruit Gro to the template (Paroush et al 1994; Fisher et al 1996; Alifragis et al 1997; Aronson et al 1997; Jimenez et al 1997; Zhang and Levine 1999). Previous studies have demonstrated that Gro/TLE family corepressors are associated with chromatin in living cells and interact with the amino-terminal tail of histone H3, suggesting that Gromediated repression may involve the modulation of local chromatin structure (Palaparti et al 1997)
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