Microarray Approaches for Analysis of Cell Cycle Regulatory Genes

Cell cycle phase-specific regulation of transcription is a major mechanism for the regulation of progress through the eukaryotic cell cycle. Hundreds of genes are known to be cell cycle regulated, including histones, cyclins, transcription factors, and genes for such cycle-specific processes as initiation of replication and cytokinesis. Many of the transcription factors involved in cell cycle regulation have been identified (Table 1 ). Many of these transcription factors and their downstream effector genes also play important roles outside of normal cell cycle progression, such as in induction of cell cycle arrest or apoptosis in response to deoxyribonucleic acid (DNA) damage or other cellular stresses. Loss of control of cell cycle-regulated genes is also known to play an important role in disease states such as genomic instability and cancer. For instance, p53, a cell cycle regulatory transcription factor, is also one of the most commonly mutated tumor-suppressor genes in human cancer (1 ), and hence one of the most exhaustively studied. Estimates based on a survey of p53 binding sites in the genome put the number of p53 regulated genes at several hundred (2 ), whereas the finding that p53 can affect the expression of some genes in the absence of direct DNA binding may increase this number (3 ). Genes known to be regulated by p53 are not restricted to roles in cell cycle progression, but are involved in other important cellular processes, such as DNA repair and apoptosis (Table 2 ). As this is an example of just one transcription factor, it is obvious that cell cycle dependent transcription involves many layers of complexity.