Cyclebase 3.0: a multi-organism database on cell-cycle regulation and phenotypes

Santos, Alberto; Wernersson, Rasmus; Jensen, Lars Juhl

doi:10.1093/nar/gku1092

Cited by 224 publications

(233 citation statements)

References 30 publications

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“…Of the 51 Rtf1-specific genes categorized into GO: 0022402 cell cycle process, 44 were downregulated by Rtf1 knockdown while 7 were upregulated by Rtf1 knockdown. A search of Cyclebase 3.0, a cell cycle-dependent gene expression database (52), indicated that 21 of the 44 downregulated genes are highly expressed in S, G 2 , and/or M phase. These findings are consistent with the idea that the 21 genes, including BUB1, CCNA2, CCNB2, CENPA, and PLK1, were downregulated through an indirect effect of an altered cell cycle.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Human Transcription Elongation Factor Rtf1: Evidence for Nonoverlapping Functions of Rtf1 and the Paf1 Complex

Cao

Yamamoto

Isobe

et al. 2015

Molecular and Cellular Biology

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bRestores TBP function 1 (Rtf1) is generally considered to be a subunit of the Paf1 complex (PAF1C), a multifunctional protein complex involved in histone modification and transcriptional or posttranscriptional regulation. Rtf1, however, is not stably associated with the PAF1C in most species except Saccharomyces cerevisiae, and its biochemical functions are not well understood. Here, we show that human Rtf1 is a transcription elongation factor that may function independently of the PAF1C. Rtf1 requires "Rtf1 coactivator" activity, which is most likely unrelated to the PAF1C or DSIF, for transcriptional activation in vitro. A mutational study revealed that the Plus3 domain of human Rtf1 is critical for its coactivator-dependent function. Transcriptome sequencing (RNA-seq) and chromatin immunoprecipitation studies in HeLa cells showed that Rtf1 and the PAF1C play distinct roles in regulating the expression of a subset of genes. Moreover, contrary to the finding in S. cerevisiae, the PAF1C was apparently recruited to the genes examined in an Rtf1-independent manner. The present study establishes a role for human Rtf1 as a transcription elongation factor and highlights the similarities and differences between the S. cerevisiae and human Rtf1 proteins. Restores TBP (TATA box-binding protein) function 1 (Rtf1) was identified as a suppressor of a TBP mutant in Saccharomyces cerevisiae (1). Subsequent genetic and biochemical studies in yeast have shown that Rtf1 functions as a component of the polymerase-associated factor 1 (Paf1) complex (PAF1C) containing Paf1, Ctr9, Leo1, and Cdc73 (2-5). The PAF1C is a multifunctional protein complex whose primary role is to facilitate histone modifications, such as H2B monoubiquitination at K123 and H3 methylation at K4 and K79 (6-12). The PAF1C also plays important roles in transcription elongation through chromatin, as well as on naked DNA (13-16). Furthermore, the PAF1C is involved in transcription termination and 3= processing of polyadenylated and nonpolyadenylated .Paf1, Ctr9, Leo1, Cdc73, and Rtf1 are highly conserved in eukaryotes; however, the subunit compositions of the PAF1C vary among species. Purification of the PAF1C from human HeLa cells yielded a five-subunit complex lacking Rtf1 but containing Ski8 as an additional subunit (22,26,27). Similarly, coimmunoprecipitation studies in zebrafish, Drosophila, and Schizosaccharomyces pombe showed that PAF1C homologs in these species lack a stably associated Rtf1 subunit (28-30). At the functional level, however, Rtf1 and other PAF1C subunits have a number of similarities. For example, knockout or knockdown of Rtf1 and other PAF1C subunits results in similar defects in histone modifications in all the species examined (27,28,31). At the organismal level, inhibition of Rtf1 and other PAF1C subunits causes similar defects in epidermal morphogenesis in Caenorhabditis elegans and in somitogenesis and cardiomyocyte development in zebrafish (29,32,33). Rtf1 and Paf1 colocalize with each other and with RNA polymerase II (RNAPII) in...

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Section: Discussionmentioning

confidence: 99%

Characterization of the Human Transcription Elongation Factor Rtf1: Evidence for Nonoverlapping Functions of Rtf1 and the Paf1 Complex

Cao

Yamamoto

Isobe

et al. 2015

Molecular and Cellular Biology

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“…Alternatively, Cdk1 substrate expression could be cell cycle regulated, in which case Cdk1 phosphorylation would provide an additional layer of regulation to fine-tune substrate function. It was previously shown by Whitfield et al (73) that of 13,912 genes profiled, 588 are cell cycle regulated (74). We mapped proteins on which we identified phosphorylation sites that responded to either Flavopiridol or RO-3306 to gene sequences present in that microarray analysis (73).…”

Section: Quantitative Analysis Of the Phosphoproteome Of Flavopiridolmentioning

confidence: 94%

Identification of Candidate Cyclin-dependent kinase 1 (Cdk1) Substrates in Mitosis by Quantitative Phosphoproteomics

Petrone

Adamo

Cheng

et al. 2016

Molecular & Cellular Proteomics

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An important objective of a cell is to accurately replicate its genetic material and evenly divide along with its subcellular components into two identical daughter cells. To do so, a cell reduces or halts growth, transcription, cap-dependent translation, and undergoes dramatic changes in cellular structure and organization. These changes include chromosome condensation, nuclear envelope breakdown, disassembly of the endoplasmic reticulum and Golgi apparatus, reorganization of the actin cortex, and the formation of the mitotic spindle. Deregulation and errors in these processes can produce nonidentical daughter cells with aberrant chromosome numbers, a state known as aneuploidy and a hallmark of human cancer and the origin of many birth defects (1-5). Therefore, it is imperative that mitosis proceeds in a highly accurate and controlled manner. This is achieved by a sophisticated network of proteins that engage in a multitude of protein-protein interactions regulated by post-translational modifications, including dynamic protein phosphorylation by protein kinases and phosphatases (summarized in (6 -8)).One of the master regulators of mitosis that is conserved from yeast to human is the cyclin-dependent kinase 1 (Cdk1) 1 (9). Cdk1 expression is constant across the cell cycle and the regulation of its activity relies on its association with cyclin A and B, as well as on post-translational modifications including phosphorylation. Specifically, mRNA and protein abundance of cyclin A and B oscillate during the cell cycle due to temporally regulated transcription, translation, and degradation cycles that restrict Cdk1 activity from S-phase to mitosis

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“…In particular, genome-wide transcriptome data provides information on the expression levels of informative cell-cycle marker genes, which have been carefully annotated in several systems and cell types (e.g., in human, yeast and Arabidopsis [16]). Consequently, we reasoned that these genes can be used to infer the cell cycle phase directly from the transcriptome.…”

Section: Introductionmentioning

confidence: 99%

Computational assignment of cell-cycle stage from single-cell transcriptome data

Scialdone

Natarajan

Saraiva

et al. 2015

Methods

393

386

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The transcriptome of single cells can reveal important information about cellular states and heterogeneity within populations of cells. Recently, single-cell RNA-sequencing has facilitated expression profiling of large numbers of single cells in parallel. To fully exploit these data, it is critical that suitable computational approaches are developed. One key challenge, especially pertinent when considering dividing populations of cells, is to understand the cell-cycle stage of each captured cell. Here we describe and compare five established supervised machine learning methods and a custom-built predictor for allocating cells to their cell-cycle stage on the basis of their transcriptome. In particular, we assess the impact of different normalisation strategies and the usage of prior knowledge on the predictive power of the classifiers. We tested the methods on previously published datasets and found that a PCA-based approach and the custom predictor performed best. Moreover, our analysis shows that the performance depends strongly on normalisation and the usage of prior knowledge. Only by leveraging prior knowledge in form of cell-cycle annotated genes and by preprocessing the data using a rank-based normalisation, is it possible to robustly capture the transcriptional cell-cycle signature across different cell types, organisms and experimental protocols.

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Cyclebase 3.0: a multi-organism database on cell-cycle regulation and phenotypes

Cited by 224 publications

References 30 publications

Characterization of the Human Transcription Elongation Factor Rtf1: Evidence for Nonoverlapping Functions of Rtf1 and the Paf1 Complex

Characterization of the Human Transcription Elongation Factor Rtf1: Evidence for Nonoverlapping Functions of Rtf1 and the Paf1 Complex

Identification of Candidate Cyclin-dependent kinase 1 (Cdk1) Substrates in Mitosis by Quantitative Phosphoproteomics

Computational assignment of cell-cycle stage from single-cell transcriptome data

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