Genome-wide analysis of transcription regulation during the cell quiescence cycle

Abstract

All organisms have cells that are capable of exiting the normal cell cycle and entering a non-proliferative state termed quiescence or G0. Most eukaryotic cells, whether they exist as single-celled or multicelular organisms, spend the majority of their life-cycle in a quiescent state. An important property of quiescent cells is that they can remain in G0 for long periods, retaining the capability to re-enter the proliferative cycle if necessary. Studying quiescence control is important for understanding cancer, development and aging. Recent developments of DNA microarray techniques facilitate studies of this common cellular state, providing tools for monitoring genome-wide regulatory effects occurring during the transition between quiescence and proliferation. We have employed several genome-wide approaches to studying the transcription regulation of quiescence in S. cerevisiae, both globally and at the gene-specific level. Our investigation (I) provides a comprehensive description of global and gene-specific mRNA expression changes associated with quiescence exit and entry, (II) shows the importance of applying appropriate normalization for microarray data (III) unravels a novel mechanism of rapid transcription activation upon exit from quiescence by poised RNA polymerase II, (IV) leads to the proposal of a two-step model for quiescence induction, (V) identifies genes and processes necessary for quiescence exit and entry, and (VI) functionally characterizes a novel gene-specific transcription regulator of the starvation response and uncovers its downstream regulatory network. In addition to these findings, this work raises several new questions and provides a framework for further exploration of the quiescent state in eukaryotes.