Mechanism of Chromatin Recognition and Transcriptional Regulation by LEF-1 and the Wnt/Wg-responsive LEF-1:β-Catenin Complex

Excerpt

The lymphoid enhancer-binding factor (LEF-1) andclosely related T-cell enhancer factor (TCF) proteins arevery potent activators of specific T-cell enhancers andalso play a key role in cell fate determination and establishment of segment polarity or dorsal–ventral axis patterning at early developmental stages in a variety of organisms (for review, see Cadigan and Nusse 1997;Clevers and van de Wetering 1997; Bienz 1998; Eastmanand Grosschedl 1999). LEF-1 is a high-mobility group(HMG) protein that is expressed broadly during development and eventually becomes restricted to pre-B and Tlymphoid cell lineages in adults (Travis et al. 1991; Oosterwegel et al. 1993; van Genderen et al. 1994; Korinek etal. 1998). The observation that LEF-1/TCF binds DNAspecifically through minor groove contacts and bendsDNA strongly (Giese et al. 1992, 1995; Love et al. 1995)has led to its classification as an architectural transcription factor (Grosschedl et al. 1994). In the decade sincewe and other investigators first purified and cloned theLEF-1/TCF proteins as lymphoid-specific transcriptionalactivators (Travis et al. 1991; van de Wetering et al. 1991;Waterman et al. 1991), a wealth of studies have established these factors as important gene-specific activatorsand repressors in different developmental contexts. Mostimportantly, the LEF-1/TCF proteins have been found tofunction as essential partners for nuclear β-catenin uponsignaling through the Wnt/Wg pathway (Behrens et al.1996; Molenaar et al. 1996; Riese et al. 1997; van de Wetering et al. 1997; Hsu et al. 1998; Korinek et al. 1998)...