Available online at www.sciencedirect.com Transcriptional control of the cell cycle Barbara Berckmans 1,2 and Lieven De Veylder 1,2 Cell division is a highly coordinated process. In the last decades, many plant cell cycle regulators have been identified. Strikingly, only a few transcriptional regulators are known, although a significant amount of the genome is transcribed in a cell cycle phase-dependent manner. E2F–DP transcription factors and three repeat MYB proteins are responsible for the expression of genes at the G1-to-S and G2-to-M transition, respectively. However, these two mechanisms cannot explain completely the transcriptional regulation seen during the cell cycle. Correspondingly, several new transcriptional regulators have been characterized, stressing the importance of transcriptional control during the cell cycle. Addresses 1 Department of Plant Systems Biology, Flanders Institute for Biotechnology (VIB), Technologiepark 927, 9052 Gent, Belgium 2 Department of Plant Biotechnology and Genetics, Ghent University, Technologiepark 927, 9052 Gent, Belgium Corresponding author: De Veylder, Lieven (lieven.deveylder@psb.vib-ugent.be) Current Opinion in Plant Biology 2009, 12:599–605 This review comes from a themed issue on Cell signalling and gene regulation Edited by Jan U. Lohmann and Jennifer L. Nemhauser Available online 21st August 2009 1369-5266/$ – see front matter # 2009 Elsevier Ltd. All rights reserved. DOI 10.1016/j.pbi.2009.07.005 Introduction The cell cycle is a tightly controlled process divided into four distinct phases. During the S and M phases, the cell replicates its genome and separates the duplicated genome over the two daughter cells, respectively. Both phases are followed by a gap phase, designated G1 and G2 [1]. It is very important that the cell cycle is regulated correctly, because mistakes that affect the genome integrity can have serious consequences for the development of the whole organism. The various cell cycle regulators that had been discovered have been integrated into models, in which the oscillating activity of cyclin-dependent kinase (CDK) com- plexes is the central control mechanism of cell cycle progression [1,2]. In these models, the cell cycle is regulated mainly at the post-transcriptional level. How- ever, transcription profiling studies of Arabidopsis thaliana cell cultures spotted more than 1000 genes that display a cell cycle-regulated expression profile [3], highlighting the significance of transcriptional regulation during cell division. Remarkably, the number of well-characterized transcription factors (TFs) with a function in the cell cycle is limited. Here we will discuss the current knowledge on the transcriptional control of the cell cycle. As cell division is part of the growth program, many developmental TFs affect somehow the cell cycle. As these TFs are discussed in different reviews [4–6], we will focus mainly on the TFs with a direct effect on the expression of cell cycle genes, namely those with an impact on the transition between the different cell cycle phases and those that control cell division entry and exit. Entry into the cell cycle Cell cycle initiation needs the stimulation of cells by different growth factors, such as cytokinins, auxins, brassi- nosteroids, sucrose, and gibberellins [1]. These mitogens trigger the production of D-type cyclins (CYCD), which, in turn, will activate CDKs during the late G1 phase [2]. However, the signal cascades inducing CYCD expression are largely unknown. Transcriptomic and chromatin immu- noprecipitation (ChIP) experiments have identified the DNA-binding with one finger (DOF) transcription factor OBP1 as an upstream regulator of CYCD3;3 (Figure 1)[7  ]. Additionally, OBP1 controls other key cell cycle genes, such as E2Fa and G2–M-specific cyclin genes (Figure 1) and, therefore, might be a general stimulator of cell divi- sion. In contrast, negative regulators of the cell cycle, such as CDK inhibitory molecules, known as Kip-related pro- teins (KRPs), are upregulated by OBP1 as well (Figure 1). This dual effect of OBP1 might possibly explain the rela- tively mild effects of OBP1 overproduction on cell division. OBP1 itself, together with CYCD1;1, was found to be a direct target of ENHANCER OF SHOOT REGENER- ATION 2 (ESR2)/BOLITA/DORNRO ¨ SCHEN-LIKE (DRNL) (Figure 1)[8], which is a TF involved in different hormonal pathways [8–10]. Overexpression of ESR2/ BOLITA/DRNL leads to enhanced shoot regeneration in the absence of cytokinins. Thus, ESR2/BOLITA/DRNL could be a downstream factor in the cytokinin-signaling pathway resulting in cell cycle induction. However, the picture is still unclear, because overexpression of ESR2/ BOLITA/DRNL reduced both cell size and cell number in a conflicting study [10]. Furthermore, a recent study on esr2/bolita/drnl knockout plants could not confirm a cell cycle effect, but showed that this particular TF more likely controls developmental pathways (Figure 1)[11]. Another TF possibly directing cytokinin signaling to the cell cycle machinery is the NAC transmembrane NTM1 www.sciencedirect.com Current Opinion in Plant Biology 2009, 12:599–605