The Global Regulatory Architecture of Transcription during the Caulobacter Cell Cycle
| Autor: | James Q. Pham, David L. Dill, Zhongying Z. Cui, Harley H. McAdams, Bo Zhou, Eduardo Abeliuk, Virginia S. Kalogeraki, Jared M. Schrader, Lucy Shapiro, Cong B. Dinh |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Transcription Genetic Gene Expression Genetic Networks Transcription (biology) Caulobacter crescentus Genes Regulator Asymmetric cell division Transcriptional regulation Promoter Regions Genetic Genetics (clinical) Genetics 0303 health sciences biology Bacterial Genomics Systems Biology Cell Cycle Microbial Growth and Development Genomics Cell cycle Bacterial Genomes Cell biology Transcriptome Analysis Research Article Protein Binding Next-Generation Sequencing lcsh:QH426-470 Microbial Genomics Genome Complexity Microbiology Caulobacter 03 medical and health sciences Gene Regulation Nucleotide Motifs Molecular Biology Transcription factor Ecology Evolution Behavior and Systematics 030304 developmental biology Bacteria Base Sequence 030306 microbiology Sequence Analysis RNA Organisms Biology and Life Sciences Computational Biology Promoter Gene Expression Regulation Bacterial Methyltransferases biology.organism_classification Genome Analysis DNA binding site lcsh:Genetics Developmental Biology |
| Zdroj: | PLoS Genetics PLoS Genetics, Vol 11, Iss 1, p e1004831 (2015) |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | Each Caulobacter cell cycle involves differentiation and an asymmetric cell division driven by a cyclical regulatory circuit comprised of four transcription factors (TFs) and a DNA methyltransferase. Using a modified global 5′ RACE protocol, we globally mapped transcription start sites (TSSs) at base-pair resolution, measured their transcription levels at multiple times in the cell cycle, and identified their transcription factor binding sites. Out of 2726 TSSs, 586 were shown to be cell cycle-regulated and we identified 529 binding sites for the cell cycle master regulators. Twenty-three percent of the cell cycle-regulated promoters were found to be under the combinatorial control of two or more of the global regulators. Previously unknown features of the core cell cycle circuit were identified, including 107 antisense TSSs which exhibit cell cycle-control, and 241 genes with multiple TSSs whose transcription levels often exhibited different cell cycle timing. Cumulatively, this study uncovered novel new layers of transcriptional regulation mediating the bacterial cell cycle. Author Summary The generation of diverse cell types occurs through two fundamental processes; asymmetric cell division and cell differentiation. Cells progress through these developmental changes guided by complex and layered genetic programs that lead to differential expression of the genome. To explore how a genetic program directs cell cycle progression, we examined the global activity of promoters at distinct stages of the cell cycle of the bacterium Caulobacter crescentus, that undergoes cellular differentiation and divides asymmetrically at each cell division. We found that approximately 21% of transcription start sites are cell cycle-regulated, driving the transcription of both mRNAs and non-coding and antisense RNAs. In addition, 102 cell cycle-regulated genes are transcribed from multiple promoters, allowing multiple regulatory inputs to control the logic of gene activation. We found combinatorial control by the five master transcription regulators that provide the core regulation for the genetic circuitry controlling the cell cycle. Much of this combinatorial control appears to be directed at refinement of temporal expression of various genes over the cell cycle, and at tighter control of asymmetric gene expression between the swarmer and stalked daughter cells. |
| Databáze: | OpenAIRE |
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