The Arabidopsis E2F Family

Arabidopsis contains a family of six E2F related proteins (Vandepoele et al. 2002). Structurally they could be divided into two distinct subgroups: the first one contains E2FA, E2FB and E2FC. These three E2Fs have all the domains conserved that are present in the animal E2F1-3, including the DNA-binding, dimerization, transactivation and RB-binding domains (Fig. 2). Members of the second group in Arabidopsis are DEL1, DEL2 and DEL3 (DP-E2F-like proteins). These are structurally related to mammalian E2F7 and E2F8 that lack all the E2F-specific domains except the DNA-binding domain, which is present in tandem duplication. Unlike E2Fs, Arabidopsis DEL DNA-binding function does not require heterodimer formation with the two known dimer-ization partner proteins, DPA and DPB (Fig. 2). The single Arabidopsis retinoblastoma-related protein (RBR1) interacts with all the three E2Fs by physically associating within their C-terminal region, but there is no known binding site for RBR1 in DELs.

Although E2Fs and DELs are clearly different in structural organization, in vitro they bind to the same DNA motif, indicating that they might compete with each other for binding to target promoter sequences. In agreement, all the E2Fs are able to transactivate on promoters containing an E2F-binding site with variable efficiency, while DELs antagonize their transcriptional activity (Kosugi and Ohashi 2002a,b; Mariconti et al. 2002). Therefore the two subgroups are functionally different; E2Fs are potentially activators while DELs are repressors. However, similarly to animal E2Fs that become re-pressors when in complex with RB proteins, due to binding to chromatin remodelling enzymes, (Rowland and Bernards 2006) Arabidopsis E2Fs are also able to interact with RBR1 protein although the function of this interaction is still unknown (de Jager et al. 2001; del Pozo et al. 2002; Magyar et al. 2005). Therefore, Arabidopsis E2Fs might work either as activators or

Fig. 2 Family of Arabidopsis E2F transcription factors. A Based on their different structural organization, the eight Arabidopsis proteins are classified into subgroup of E2Fs, DPs and DELs (Vandepoele et al. 2002). B Deletion mutants of E2FC and DPA used as molecular tools for studying E2F functions (del Pozo et al. 2002, 2006; Ramirez-Parra et al. 2003; Magyar and DeVeylder, unpublished results)

Fig. 2 Family of Arabidopsis E2F transcription factors. A Based on their different structural organization, the eight Arabidopsis proteins are classified into subgroup of E2Fs, DPs and DELs (Vandepoele et al. 2002). B Deletion mutants of E2FC and DPA used as molecular tools for studying E2F functions (del Pozo et al. 2002, 2006; Ramirez-Parra et al. 2003; Magyar and DeVeylder, unpublished results)

repressors depending on their association with RB, while DELs could be re-pressors or "anti-repressors" antagonizing with both types of E2F complexes on target promoters. Consequently, one would expect that modulating the expression of DELs in plants could change the activity of cell proliferation. However, the currently available data, rather than supporting a role for regulation of cell division, indicates that DELs might have specific roles in cell growth and expansion since loss of function or ectopic expression of DEL1 or DEL3 resulted in fairly normal-looking Arabidopsis plants (Ramirez-Parra et al. 2004; Vlieghe et al. 2005). Furthermore, variation of DEL3 levels lead to misexpression of E2F target genes unrelated to cell cycle but involved in cell wall biogenesis (Ramirez-Parra et al. 2004). DEL1 was found to influence ploidy level; loss of function dell increased the DNA amount while ectopic DEL1 repressed it, indicating a specific role for this transcription factor in the regulation of endoreduplication. Correspondingly, there was a correlation between the expressions ofsome S-phase regulated E2F target genes (e.g. CDC6, MCM3) and the level of DEL1 in the cotyledons (Vlieghe et al. 2005). Altogether, DEL1 could be an "anti-repressor" with a function to antagonize an E2F-dependent repression of mitotic cell cycle and thus act on the develop-mentally regulated switch from mitosis to endocycle. However, the idea that DELs could antagonize all the E2F complexes on target promoters is questionable, since the ectopic expression of DEL1 could not suppress the ectopic cell divisions caused by the simultaneous overexpression of both E2FA and DPA (Vlieghe et al. 2005).

On the basis of these data it was suggested that DELs and E2Fs could have different target specificities and/or that they compete with each other for binding to promoter sequences on only a subset of E2F target genes. In this respect it is worth mentioning that the mechanism governing the selectivity of E2F-promoter interaction is more complex than a simple E2F-DNA recognition as we know in animal cells (Zhu et al. 2005). The DNA-binding specificity of E2F has been attributed to protein interactions mediated by the marked box domain (Black et al. 2005). Plant E2Fs contain a similar domain, but DELs are missing it (Fig. 2), indicating that the target specificity of Arabidopsis E2Fs and DELs could be directed via protein interactions to distinct promoters.

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