The Central Role of CDE/CHR Promoter Elements in the Regulation of Cell Cycle-dependent Gene Transcription

The cell cycle-dependent element (CDE) and the cell cycle genes homology region (CHR) control the transcription of genes with maximum expression in G(2) phase and in mitosis. Promoters of these genes are repressed by proteins binding to CDE/CHR elements in G(0) and G(1) phases. Relief from repression begins in S phase and continues into G(2) phase and mitosis. Generally, CDE sites are located four nucleotides upstream of CHR elements in TATA-less promoters of genes such as Cdc25C, Cdc2 and cyclin A. However, expression of some other genes, such as human cyclin B1 and cyclin B2, has been shown to be controlled only by a CHR lacking a functional CDE. To date, it is not fully understood which proteins bind to and control CDE/CHR-containing promoters. Recently, components of the DREAM complex were shown to be involved in CDE/CHR-dependent transcriptional regulation. In addition, the expression of genes regulated by CDE/CHR elements is mostly achieved through CCAAT-boxes, which bind heterotrimeric NF-Y proteins as well as the histone acetyltransferase p300. Importantly, many CDE/CHR promoters are downregulated by the tumor suppressor p53. In this review, we define criteria for CDE/CHR-regulated promoters and propose to distinguish two classes of CDE/CHR-regulated genes. The regulation through transcription factors potentially binding to the CDE/CHR is discussed, and recently discovered links to central pathways regulated by E2F, the pRB family and p53 are highlighted.