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Sci Aging Knowledge Environ,
2005]
Several recent studies have highlighted how RNA interference has advanced aging-related research in Caenorhabditis elegans. Two new genome-wide RNAi-based screens together identified more than 100 new candidate longevity genes. RNAi has also greatly facilitated the functional validation of several large-scale gene expression profiling studies. Furthermore, RNAi is flexible and can be administered at different times throughout life; this feature has been exploited to analyze the temporal requirement of genes in life-span determination.
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Exp Gerontol,
2006]
This article discusses the pros and cons of using RNAi screening to identify longevity genes in Caenorhabditis elegans. The discussion will focus on the results of two large-scale longevity RNAi screens that were recently published. The two screens revealed largely non-overlapping sets of candidate longevity genes. The possible reasons for such differences and their implications will be discussed.
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Front Mol Biosci,
2023]
Aging affects nearly all aspects of our cells, from our DNA to our proteins to how our cells handle stress and communicate with each other. Age-related chromatin changes are of particular interest because chromatin can dynamically respond to the cellular and organismal environment, and many modifications at chromatin are reversible. Changes at chromatin occur during aging, and evidence from model organisms suggests that chromatin factors could play a role in modulating the aging process itself, as altering proteins that work at chromatin often affect the lifespan of yeast, worms, flies, and mice. The field of chromatin and aging is rapidly expanding, and high-resolution genomics tools make it possible to survey the chromatin environment or track chromatin factors implicated in longevity with precision that was not previously possible. In this review, we discuss the state of chromatin and aging research. We include examples from yeast, <i>Drosophila</i>, mice, and humans, but we particularly focus on the commonly used aging model, the worm <i>Caenorhabditis elegans</i>, in which there are many examples of chromatin factors that modulate longevity. We include evidence of both age-related changes to chromatin and evidence of specific chromatin factors linked to longevity in core histones, nuclear architecture, chromatin remodeling, and histone modifications.
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Brief Funct Genomics,
2010]
Our understanding of the genetic mechanisms of organismal aging has advanced dramatically during the past two decades. With the development of large-scale RNAi screens, the last few years saw the remarkable identifications of hundreds of new longevity genes in the roundworm Caenorhabditis elegans. The various RNAi screens revealed many biological pathways previously unknown to be related to aging. In this review, we focus on findings from the recent large-scale RNAi longevity screens, and discuss insights they have provided into the complex biological process of aging and considerations of the RNAi technology will continue to have on the future development of the aging field.
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Bioessays,
2008]
Predicting the phenotype of an organism from its genotype is a central question in genetics. Most importantly, we would like to find out if the perturbation of a single gene may be the cause of a disease. However, our current ability to predict the phenotypic effects of perturbations of individual genes is limited. Network models of genes are one tool for tackling this problem. In a recent study, (Lee et al.) it has been shown that network models covering the majority of genes of an organism can be used for accurately predicting phenotypic effects of gene perturbations in multicellular organisms. BioEssays 30:707-710, 2008. (c) 2008 Wiley Periodicals, Inc.
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1980]
A number of review articles on the nematode cuticle have been published in the last decade. The most recent of these are those of Bird and Lee and Atkinson. These authors, while emphasizing the complexity and variability of nematode cuticles, support the use of a simplified nomenclature of cuticle structure which divides the cuticle into three regions or zones-namely, cortical, median, and basal. It is obvious that many exceptions to this fundamental pattern occur, and I shall mention some of these below. However, I think that they are adaptations to survival in changing environments, particularly where parasitism is involved. In particular, I propose to consider the structure and functions of the surface or epicuticle of the cortical zone, for it is here that reactions similar to those occurring at cell surfaces and in cell membranes are thought to occur in a wide range of "helminth" organisms. At the moment, particularly for the Nematoda, these ideas require more experimental evidence to establish them as facts. However, the use of sensitive techniques currently employed by membrane physicists and chemists to isolate, label, analyze, measure, and observe interactions taking place in cell membranes have in many instances yet to be used on the nematode cuticle. There is no doubt that the free-living bacterial-feeding nematodes such as those belonging to the genus Caenorhabditis, and in particular C. elegans, are the experimental models of choice for this purpose.
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Crit Rev Biochem Mol Biol,
2012]
The CCAAT box promoter element and NF-Y, the transcription factor (TF) that binds to it, were among the first cis-elements and trans-acting factors identified; their interplay is required for transcriptional activation of a sizeable number of eukaryotic genes. NF-Y consists of three evolutionarily conserved subunits: a dimer of NF-YB and NF-YC which closely resembles a histone, and the "innovative" NF-YA. In this review, we will provide an update on the functional and biological features that make NF-Y a fundamental link between chromatin and transcription. The last 25 years have witnessed a spectacular increase in our knowledge of how genes are regulated: from the identification of cis-acting sequences in promoters and enhancers, and the biochemical characterization of the corresponding TFs, to the merging of chromatin studies with the investigation of enzymatic machines that regulate epigenetic states. Originally identified and studied in yeast and mammals, NF-Y - also termed CBF and CP1 - is composed of three subunits, NF-YA, NF-YB and NF-YC. The complex recognizes the CCAAT pentanucleotide and specific flanking nucleotides with high specificity (Dorn et al., 1997; Hatamochi et al., 1988; Hooft van Huijsduijnen et al, 1987; Kim & Sheffery, 1990). A compelling set of bioinformatics studies clarified that the NF-Y preferred binding site is one of the most frequent promoter elements (Suzuki et al., 2001, 2004; Elkon et al., 2003; Marino-Ramirez et al., 2004; FitzGerald et al., 2004; Linhart et al., 2005; Zhu et al., 2005; Lee et al., 2007; Abnizova et al., 2007; Grskovic et al., 2007; Halperin et al., 2009; Hakkinen et al., 2011). The same consensus, as determined by mutagenesis and SELEX studies (Bi et al., 1997), was also retrieved in ChIP-on-chip analysis (Testa et al., 2005; Ceribelli et al., 2006; Ceribelli et al., 2008; Reed et al., 2008). Additional structural features of the CCAAT box - position, orientation, presence of multiple Transcriptional Start Sites - were previously reviewed (Dolfini et al., 2009) and will not be considered in detail here.