Essential genes

Kemphues, Kenneth J.

doi:10.1895/wormbook.1.57.1

Cited by 28 publications

(23 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Screens to identify genes that are key to maintaining the ES cell state have identified only a small number of all of the transcription factor genes that are expressed in these cells (Ivanova et al 2006; Zhang et al 2006; Fazzio et al 2008). Furthermore, several studies have shown that many transcription factors can be eliminated without dire consequences for the cell (Winzeler et al 1999; Giaever et al 2002; Kemphues 2005). The small set of transcription factors that have been demonstrated to be important for establishment or maintenance of a cell state will henceforth be termed “key regulators.”…”

Section: Concept Of Core Transcriptional Regulatory Circuitrymentioning

confidence: 99%

Mapping Key Features of Transcriptional Regulatory Circuitry in Embryonic Stem Cells

Cole¹,

Young²

2008

Cold Spring Harbor Symposia on Quantitative Biology

View full text Add to dashboard Cite

The process by which a single fertilized egg develops into a human being with more than 200 cell types-each with a distinct gene expression pattern controlling its cellular state-is poorly understood. Knowledge of the transcriptional regulatory circuitry that establishes and maintains gene expression programs in mammalian cells is fundamental to understanding development and should provide the foundation for improved diagnosis and treatment of disease. Although it is not yet feasible to map the entirety of this circuitry in vertebrate cells, recent work in embryonic stem (ES) cells has demonstrated that core features of the circuitry can be discovered through studies involving selected regulators. Here, we highlight the fundamental insights that have emerged from studies that examined the role of transcription factors, chromatin regulators, signaling pathways, and noncoding RNAs in the regulatory circuitry of ES cells. Maps of regulatory circuitry and the insights that have emerged from these studies have improved our understanding of global gene expression and are facilitating efforts to reprogram cells for disease therapeutics and regenerative medicine. also thought to be important for maintaining gene expression programs associated with specific cell states; Trithorax group complexes are associated with actively transcribed genes, whereas Polycomb group regulators are associated with repression of most genes that they occupy (Pirrotta 1998;Orlando 2003;Ringrose and Paro 2004;Schuettengruber et al. 2007;Schwartz and Pirrotta 2007).Signaling pathways act to maintain or initiate changes in the regulatory circuitry in response to environmental or developmental cues. The terminal components of signaling pathways are often protein kinases that can phosphorylate and activate transcriptional regulators or are themselves transcription factors and chromatin modifiers (Hunter 2000;Brivanlou and Darnell 2002;Yang et al. 2003;Pokholok et al. 2006 (Verdel et al. 2004;Moazed et al. 2006;Grewal and Elgin 2007;Rinn et al. 2007;Zaratiegui et al. 2007). We have limited understanding of the regulation of expression of noncoding RNA species, and in most cases, we have yet to identify the specific set of genes that are under the control of these noncoding RNA species. CONCEPT OF CORE TRANSCRIPTIONAL REGULATORY CIRCUITRYHundreds of gene expression regulators are present in each cell, making it a challenge to map the regulatory network that they form in even one cell type, much less in 200 cell types (Lander et al. 2001;Brivanlou and Darnell 2002). For this reason, even the most ambitious global studies have examined only a handful of transcriptional regulators and then in only a few cell types (Cawley et al. 2004;Odom et al. 2004Odom et al. , 2006Boyer et al. 2005; RadaIglesias et al. 2005 RadaIglesias et al. , 2008Loh et al. 2006;Barski et al. 2007;Mikkelsen et al. 2007;Chen et al. 2008;Cole et al. 2008;Jaenisch and Young 2008;Jiang et al. 2008;Kim et al. 2008a;Komashko et al. 2008;Marson et al. 2008b;Park et al. 2008;Reed et al....

show abstract

Section: Concept Of Core Transcriptional Regulatory Circuitrymentioning

confidence: 99%

Mapping Key Features of Transcriptional Regulatory Circuitry in Embryonic Stem Cells

Cole¹,

Young²

2008

Cold Spring Harbor Symposia on Quantitative Biology

View full text Add to dashboard Cite

show abstract

“…The details of this association will be interesting and enlightening with regard to the evolutionary and ecological capacity of this premier model system and may expand our functional understanding of its genome. In this context it is interesting to consider the fact that, as with all model organisms, a large fraction of the C. elegans genome remains functionally uncharacterized, the number of essential genes under normal laboratory conditions is small (<30%) compared with the total number of genes encoded and evolutionarily conserved, and a large fraction of the functional knockouts have no detectable phenotype in typical laboratory culture (Kamath et al, 2003;Kemphues, 2005). Genetic redundancy and incomplete phenotypic characterization can explain some fraction of the uncharacterized genome.…”

Section: Resultsmentioning

confidence: 99%

“…For the first set of experiments cultures of each nematode strain were switched to growth on SCBI after standard bleaching and starvation of L1 (Kemphues, 2005). Each nematode strain was subsequently maintained on NGM plates seeded with Serratia sp.…”

Section: Nematode Penetration and Reproduction In Galleriamentioning

confidence: 99%

An entomopathogenic Caenorhabditis briggsae

Abebe

Jumba

Bonner

et al. 2010

Journal of Experimental Biology

View full text Add to dashboard Cite

SUMMARY Caenorhabditis elegans is a premier model organism upon which considerable knowledge of basic cell and developmental biology has been built. Yet, as is true for many traditional model systems, we have limited knowledge of the ecological context in which these systems evolved, severely limiting our understanding of gene function. A better grasp of the ecology of model systems would help us immensely in understanding the functionality of genes and evolution of genomes in an environmental context. Consequently, there are ongoing efforts to uncover natural populations of this model system globally. Here, we describe the discovery of a Caenorhabditis briggsae strain and its bacterial associate (Serratia sp.) that form an entomopathogenic complex in the wild. Laboratory experiments confirm that this nematode and its natural bacterial associate can penetrate, kill and reproduce in an insect host and that the bacterial associate can induce this insect pathogenic life cycle in other Caenorhabditis species, including C. elegans. Our findings suggest that this life history may be widespread in nature and critical to the understanding of the biology of this important model organism. Caenorhabditis–insect interaction could be a key factor in our quest for a better grasp of gene functionality in this important model species. The discovered association, consequently, would provide an ecological framework for functional genomics of Caenorhabditis.

show abstract

“…Identifying requirements for nonessential genes: While mutational studies and genomewide RNAi screens in C. elegans have identified thousands of genes that either are essential or have visible requirements, 70% of the known and predicted genes in C. elegans have no known requirements (Kemphues 2005), even though at least half have homologs in other animal phyla (Lander et al 2001). Identifying roles for conserved but nonessential genes in essential processes is an important frontier of genetic research in model organisms, as many such genes could be relevant to human disease processes.…”

Section: Discussionmentioning

confidence: 99%

Using RNA Interference to Identify Specific Modifiers of a Temperature-Sensitive, Embryonic-Lethal Mutation in the Caenorhabditis elegans Ubiquitin-Like Nedd8 Protein Modification Pathway E1-Activating Gene rfl-1

Dorfman

Gomes²,

O’Rourke³

et al. 2009

Genetics

View full text Add to dashboard Cite

The essential Caenorhabditis elegans gene rfl-1 encodes one subunit of a heterodimeric E1-activating enzyme in the Nedd8 ubiquitin-like protein conjugation pathway. This pathway modifies the Cullin scaffolds of E3 ubiquitin ligases with a single Nedd8 moiety to promote ligase function. To identify genes that influence neddylation, we used a synthetic screen to identify genes that, when depleted with RNAi, enhance or suppress the embryonic lethality caused by or198ts, a temperature-sensitive (ts) mutation in rfl-1. We identified reproducible suppressor and enhancer genes and employed a systematic specificity analysis for each modifier using four unrelated ts embryonic lethal mutants. Results of this analysis highlight the importance of specificity controls in identifying genetic interactions relevant to a particular biological process because 8/14 enhancers and 7/21 suppressors modified lethality in other mutants. Depletion of the strongest specific suppressors rescued the early embryonic cell division defects in rfl-1(or198ts) mutants. RNAi knockdown of some specific suppressors partially restored Cullin neddylation in rfl-1(or198ts) mutants, consistent with their gene products normally opposing neddylation, and GFP fusions to several suppressors were detected in the cytoplasm or the nucleus, similar in pattern to Nedd8 conjugation pathway components in early embryonic cells. In contrast, depletion of the two strongest specific enhancers did not affect the early embryonic cell division defects observed in rfl-1(or198ts) mutants, suggesting that they may act at later times in other essential processes. Many of the specific modifiers are conserved in other organisms, and most are nonessential. Thus, when controlled properly for specificity, modifier screens using conditionally lethal C. elegans mutants can identify roles for nonessential but conserved genes in essential processes.

show abstract

Essential genes

Cited by 28 publications

References 11 publications

Mapping Key Features of Transcriptional Regulatory Circuitry in Embryonic Stem Cells

Mapping Key Features of Transcriptional Regulatory Circuitry in Embryonic Stem Cells

An entomopathogenic Caenorhabditis briggsae

Using RNA Interference to Identify Specific Modifiers of a Temperature-Sensitive, Embryonic-Lethal Mutation in the Caenorhabditis elegans Ubiquitin-Like Nedd8 Protein Modification Pathway E1-Activating Gene rfl-1

Contact Info

Product

Resources

About