28 P. Doerner
characterize cell cycle phase-specific expression in free-running cells, which
is ultimately the most valid approach.
4.2
Identification of Motifs
Much effort and hope has been invested into the in silico discovery of shared
regulatory motifs in co-regulated genes with the aim of using these to iden-
tify the cognate transcriptional regulators. The early methods just took the
promoter sequences of gene arrays into account, but more recently developed
programs provide the option to include expression data (i.e. to restrict the an-
alysis to co-regulated genes) and to exclude motifs present in promoters of
genes expressed at other cell cycle phases (see, for example, WORDSPY: Wang
et al. 2005; Wang and Zhang 2006). The diverse approaches have recently been
comparatively evaluated (not including more recent programs: Tompa et al.
2005); the bottom-line is that when using real data sets, these computational
approaches to dissecting gene regulatory networks are still far from being
predictive and convincing starting points for experimental validation.
4.3
Novel Experiments: Accessing the Entire Regulatory Space
Since the various regulatory networks controlling cell cycle progression inter-
sect and are coupled, it is not surprising that transcriptional control of key
transcriptional regulators involved in periodic gene expression is only one
avenue for their regulation. Numerous examples from plant, yeast and ani-
mal systems show that post-translational control mechanisms play important
roles in controlling their activity (Bähler 2005; Inze and Veylder 2006; Mor-
gan 2007). Therefore, systems-wide approaches to concomitantly determine
not only changes to transcript abundance, but also to phosphorylation, reg-
ulated subcellular localization and regulated protein stability (to name just
a few) will be crucial for experimental strategies to identify the components
and functional logic of gene regulatory networks that governs periodic gene
expression during the plant cell cycle.
5
Conclusions and Perspectives
Recent conceptual advances and experimental data suggest that the conven-
tional, hierarchical view of cell cycle control has reached the limit of its utility.
This view, in which the oscillations of CDK/cyclin activity are considered to be
at the nexus of cell cycle control, with periodic bursts of proteolytic activity
and transcription factor activity acting as enforcers of cell cycle phase tran-