The WD repeats of Tup1 interact with the homeo domain protein alpha 2.

Abstract

Tupl and Ssn6 transcriptionally repress a wide variety of genes in yeast but do not appear to bind DNA. We provide genetic and biochemical evidence that the DNA-binding protein a2, a regulator of cell-type-specific genes, recruits the Tupl/Ssn6 repressor by directly interacting with Tupl. This interaction is mediated by a region of Tupl containing seven copies of the WD repeat, a 40 amino acid motif of unknown function found in many other proteins. We have found that a single WD repeat will interact with a2, indicating that the WD repeat is a protein-protein interaction domain. Furthermore, a fragment of Tupl containing primarily WD repeats provides at least partial repression in the absence of Ssn6, suggesting that the repeats also mediate interaction between Tupl and other components of the repression machinery.

Mutations in the FIE and MEA Genes That Encode Interacting Polycomb Proteins Cause Parent-of-Origin Effects on Seed Development by Distinct Mechanisms

“…The WD repeats in this family of proteins form a circular structure known as a ␤-propeller, which forms surface loops used as a scaffold for the generation of protein complexes (Komachi et al, 1994;Wall et al, 1995;Sondek et al, 1996). The closest related members to FIE in model genetic organisms are the polycomb proteins ESC in Drosophila (Sathe and Harte, 1995), EED in mouse (Schumacher et al, 1996), and MES6 in Caenorhabditis (Korf et al, 1998 (Jones et al, 1998;Tie et al, 1998).…”

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

“…WD40 repeats generally function as protein-protein interaction domains and have been shown to form a ␤-propeller structure in which each repeat projects outward radially and is available for interactions with other proteins (Neer et al 1994;Sondek et al 1996). For example, the WD40 repeats of the yeast TUP1 protein make direct contacts with the homeodomain protein alpha2 (Komachi et al 1994;Komachi and Johnson 1997). The WD40 repeats of Groucho appear to be involved in making contact with Engrailed and Hairy as deletion of all of the repeats eliminates the interaction with these proteins (Jimenez et al 1997).…”

“…First, although the Groucho proteins and TUP1 both act as corepressors for members of multiple families of transcription factors, many of the DNA-binding partners for TUP1 do not directly interact with TUP1, but instead utilize an accessory protein known as CYC8 to form a stable complex (Keleher et al 1992;Tzamarias and Struhl 1995). In contrast to the Groucho proteins, which directly bind all currently studied partners, TUP1 directly binds only one DNA-binding partner, the ␣2 protein (Komachi et al 1994;Komachi and Johnson 1997). Second, both TUP1 and the Groucho proteins have intrinsic repressor activity, and for TUP1 this activity appears to be mediated both by direct inhibition of the basal complex, perhaps via direct interaction with the RNA polymerase II-associated Srb proteins (Herschbach et al 1994;Wahi and Johnson 1995;Carlson 1997;Redd et al 1997), and by interaction with histones H3 and H4 (Edmondson et al 1996).…”

Activators and repressors: making use of chromatin to regulate transcription

“…Tup1p is a 713 amino acid protein: the C-terminal domain contains eight repeats of a 43 amino acid sequence rich in aspartate and tryptophan (WD-40) repeats (Fong et al 1986). These WD-40 repeats facilitate the targeting of TUP1p to particular promoters through interaction with the DNA sequencespecific a2 repressor (MATa2p) (Komachi et al 1994). The N-terminal domain of TUP1p also interacts with proteins.…”