Download or read book Spatio Temporal Regulation of Cell Cycle Transcription written by Umut Eser and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The Start checkpoint regulates cell cycle commitment and associated transcription in the budding yeast, Saccharomyces cerevisiae. It was previously shown that commitment to cell division corresponds to activating the positive feedback loop of G1 cyclins controlled by the transcription factors SBF and MBF. Around this pivotal cell cycle event, over 300 genes (G1/S regulon) are expressed to facilitate the G1/S transition. Despite its importance, little was known about distinct temporal regulation within the G1/S regulon. We found that SBF and MBF target genes have a well-defined distribution of transcriptional activation times. We also showed that activation of G1 cyclins precedes the activation of the bulk of the G1/S regulon, which we named 'feedback-first' regulation. In budding yeast, feedback-first regulation ensures that commitment to cell division occurs before large-scale changes in transcription. Thus, the transition can be viewed as a two-step process whereby the decision to divide precedes synthesis of the cellular machinery required for division. Furthermore, we found that feedback-first regulation is conserved in the related yeast S. bayanus as well as human cells. This finding highlighted the importance of understanding the molecular mechanisms through which co-regulated genes can have distinct activation dynamics. We showed that timing is partially explained by the combinatorial use of SBF and MBF transcription factors, which implement a logical OR function for gene activation. In addition to combinatorial use of transcription factors, we analyzed genome-wide chromosome conformation capture data to examine the potential link between the timing of gene expression and 3-D genome architecture. The early-activated genes of the G1/S regulon are significantly enriched for the number of physical contacts to the rest of the genome. Further analysis revealed two main clusters, whose interactions co-vary and whose activation time distributions are distinct. Taken together, these our work explains a significant amount of timing variation within cell cycle-dependent gene expression. Thus, we concluded that the cell utilizes both genome architecture and the combinatorial use of transcription factors to implement feedback-first regulation ensuring that commitment to cell division precedes genome-wide cell cycle-dependent transcription.