Abstract:
:In C. elegans, removal of the germline extends lifespan significantly. We demonstrate that the nuclear hormone receptor, NHR-49, enables the response to this physiological change by increasing the expression of genes involved in mitochondrial β-oxidation and fatty-acid desaturation. The coordinated augmentation of these processes is critical for germline-less animals to maintain their lipid stores and to sustain de novo fat synthesis during adulthood. Following germline ablation, NHR-49 is up-regulated in somatic cells by the conserved longevity determinants DAF-16/FOXO and TCER-1/TCERG1. Accordingly, NHR-49 overexpression in fertile animals extends their lifespan modestly. In fertile adults, nhr-49 expression is DAF-16/FOXO and TCER-1/TCERG1 independent although its depletion causes age-related lipid abnormalities. Our data provide molecular insights into how reproductive stimuli are integrated into global metabolic changes to alter the lifespan of the animal. They suggest that NHR-49 may facilitate the adaptation to loss of reproductive potential through synchronized enhancement of fatty-acid oxidation and desaturation, thus breaking down some fats ordained for reproduction and orchestrating a lipid profile conducive for somatic maintenance and longevity.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Ratnappan R,Amrit FR,Chen SW,Gill H,Holden K,Ward J,Yamamoto KR,Olsen CP,Ghazi Adoi
10.1371/journal.pgen.1004829subject
Has Abstractpub_date
2014-12-04 00:00:00pages
e1004829issue
12eissn
1553-7390issn
1553-7404pii
PGENETICS-D-14-01216journal_volume
10pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::Krüppel-associated box domain-zinc finger proteins (KRAB-ZFPs) are tetrapod-specific transcriptional repressors encoded in the hundreds by the human genome. In order to explore their as yet ill-defined impact on gene expression, we developed an ectopic repressor assay, allowing the study of KRAB-mediated transcription...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000869
更新日期:2010-03-05 00:00:00
abstract::The semidominant Danforth's short tail (Sd) mutation arose spontaneously in the 1920s. The homozygous Sd phenotype includes severe malformations of the axial skeleton with an absent tail, kidney agenesis, anal atresia, and persistent cloaca. The Sd mutant phenotype mirrors features seen in human caudal malformation sy...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003205
更新日期:2013-01-01 00:00:00
abstract::In flat-faced dog breeds, air resistance caused by skull conformation is believed to be a major determinant of Brachycephalic Obstructive Airway Syndrome (BOAS). The clinical presentation of BOAS is heterogeneous, suggesting determinants independent of skull conformation contribute to airway disease. Norwich Terriers,...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008102
更新日期:2019-05-16 00:00:00
abstract::Dishevelled (Dvl) proteins are important signaling components of both the canonical beta-catenin/Wnt pathway, which controls cell proliferation and patterning, and the planar cell polarity (PCP) pathway, which coordinates cell polarity within a sheet of cells and also directs convergent extension cell (CE) movements t...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000259
更新日期:2008-11-01 00:00:00
abstract::The oligodendrocyte density is greater and myelin sheaths are thicker in the adult male mouse brain when compared with females. Here, we show that these sex differences emerge during the first 10 postnatal days, precisely at a stage when a late wave of oligodendrocyte progenitor cells arises and starts differentiating...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007049
更新日期:2017-11-06 00:00:00
abstract::We resequenced and phased 27 kb of DNA within 580 kb of the MHC class II region in 158 population chromosomes, most of which were conserved extended haplotypes (CEHs) of European descent or contained their centromeric fragments. We determined the single nucleotide polymorphism and deletion-insertion polymorphism allel...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004637
更新日期:2014-10-09 00:00:00
abstract::In understanding the etiology of breast cancer, the contributions of both genetic and environmental risk factors are further complicated by the impact of breast developmental stage. Specifically, the time period ranging from childhood to young adulthood represents a critical developmental window in a woman's life when...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006261
更新日期:2016-08-18 00:00:00
abstract::Perennial questions of evolutionary biology can be applied to gene regulatory systems using the abundance of experimental data addressing gene regulation in a comparative context. What is the tempo (frequency, rate) and mode (way, mechanism) of transcriptional regulatory evolution? Here we synthesize the results of 23...
journal_title:PLoS genetics
pub_type: 杂志文章,评审
doi:10.1371/journal.pgen.1002432
更新日期:2012-01-01 00:00:00
abstract::Sodalis glossinidius, a maternally inherited endosymbiont of the tsetse fly, maintains genes encoding homologues of the PhoP-PhoQ two-component regulatory system. This two-component system has been extensively studied in facultative bacterial pathogens and is known to serve as an environmental magnesium sensor and a r...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002349
更新日期:2011-11-01 00:00:00
abstract::The genetic background of complex diseases is proposed to consist of several low-penetrance risk loci. Addressing this complexity likely requires both large sample size and simultaneous analysis of different predisposing variants. We investigated the role of four thrombosis genes: coagulation factor V (F5), intercellu...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0030120
更新日期:2007-07-01 00:00:00
abstract::In non-motile fungi, sexual reproduction relies on strong morphogenetic changes in response to pheromone signaling. We report here on a systematic screen for morphological abnormalities of the mating process in fission yeast Schizosaccharomyces pombe. We derived a homothallic (self-fertile) collection of viable deleti...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006721
更新日期:2017-04-14 00:00:00
abstract::Accurate methods to assess the pathogenicity of mutations are needed to fully leverage the possibilities of genome sequencing in diagnosis. Current data-driven and bioinformatics approaches are, however, limited by the large number of new variations found in each newly sequenced genome, and often do not provide direct...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006739
更新日期:2017-04-19 00:00:00
abstract::Capsules allow bacteria to colonize novel environments, to withstand numerous stresses, and to resist antibiotics. Yet, even though genetic exchanges with other cells should be adaptive under such circumstances, it has been suggested that capsules lower the rates of homologous recombination and horizontal gene transfe...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007862
更新日期:2018-12-21 00:00:00
abstract::Postembryonic development in Caenorhabditis elegans is a powerful model for the study of the temporal regulation of development and for the roles of microRNAs in controlling gene expression. Stable switch-like changes in gene expression occur during development as stage-specific microRNAs are expressed and subsequentl...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005099
更新日期:2015-03-27 00:00:00
abstract::The DREAM (Dp/Retinoblastoma(Rb)-like/E2F/MuvB) transcriptional repressor complex acts as a gatekeeper of the mammalian cell cycle by establishing and maintaining cellular quiescence. How DREAM's three functional components, the E2F-DP heterodimer, the Rb-like pocket protein, and the MuvB subcomplex, form and function...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007088
更新日期:2017-11-01 00:00:00
abstract::Domestic dog breeds exhibit remarkable morphological variations that result from centuries of artificial selection and breeding. Identifying the genetic changes that contribute to these variations could provide critical insights into the molecular basis of tissue and organismal morphogenesis. Bulldogs, French Bulldogs...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007850
更新日期:2018-12-06 00:00:00
abstract::Mimulus guttatus and M. nasutus are an evolutionary and ecological model sister species pair differentiated by ecology, mating system, and partial reproductive isolation. Despite extensive research on this system, the history of divergence and differentiation in this sister pair is unclear. We present and analyze a po...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004410
更新日期:2014-06-26 00:00:00
abstract::Sexual dimorphisms in trait expression are widespread among animals and are especially pronounced in ornaments and weapons of sexual selection, which can attain exaggerated sizes. Expression of exaggerated traits is usually male-specific and nutrition sensitive. Consequently, the developmental mechanisms generating se...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004098
更新日期:2014-01-01 00:00:00
abstract::Populations in sub-Saharan Africa have historically been exposed to intense selection from chronic infection with falciparum malaria. Interestingly, populations with the highest malaria intensity can be identified by the increased occurrence of endemic Burkitt Lymphoma (eBL), a pediatric cancer that affects population...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008027
更新日期:2019-03-08 00:00:00
abstract::Hypercholesterolemia is a causal and modifiable risk factor for atherosclerotic cardiovascular disease. A critical pathway regulating cholesterol homeostasis involves the receptor-mediated endocytosis of low-density lipoproteins into hepatocytes, mediated by the LDL receptor. We applied genome-scale CRISPR screening t...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1009285
更新日期:2021-01-29 00:00:00
abstract::Genetic disruption of the dystrophin complex produces muscular dystrophy characterized by a fragile muscle plasma membrane leading to excessive muscle degeneration. Two genetic modifiers of Duchenne Muscular Dystrophy implicate the transforming growth factor β (TGFβ) pathway, osteopontin encoded by the SPP1 gene and l...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007070
更新日期:2017-10-24 00:00:00
abstract::Both genetic and epigenetic alterations contribute to Facio-Scapulo-Humeral Dystrophy (FSHD), which is linked to the shortening of the array of D4Z4 repeats at the 4q35 locus. The consequence of this rearrangement remains enigmatic, but deletion of this 3.3-kb macrosatellite element might affect the expression of the ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000394
更新日期:2009-02-01 00:00:00
abstract::In the enterobacterial species Escherichia coli and Salmonella enterica, expression of horizontally acquired genes with a higher than average AT content is repressed by the nucleoid-associated protein H-NS. A classical example of an H-NS-repressed locus is the bgl (aryl-beta,D-glucoside) operon of E. coli. This locus ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000405
更新日期:2009-03-01 00:00:00
abstract::Movement of the transcription machinery along a template alters DNA topology resulting in the accumulation of supercoils in DNA. The positive supercoils generated ahead of transcribing RNA polymerase (RNAP) and the negative supercoils accumulating behind impose severe topological constraints impeding transcription pro...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006754
更新日期:2017-05-02 00:00:00
abstract::Human neutrophil antigen 2 (HNA-2) deficiency is a common phenotype as 3-5% humans do not express HNA-2. HNA-2 is coded by CD177 gene that associates with human myeloproliferative disorders. HNA-2 deficient individuals are prone to produce HNA-2 alloantibodies that cause a number of disorders including transfusion-rel...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005255
更新日期:2015-05-29 00:00:00
abstract::Iran, despite its size, geographic location and past cultural influence, has largely been a blind spot for human population genetic studies. With only sparse genetic information on the Iranian population available, we pursued its genome-wide and geographic characterization based on 1021 samples from eleven ethnic grou...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008385
更新日期:2019-09-24 00:00:00
abstract::Autosomal dominant polycystic kidney disease (ADPKD) is characterized by formation of renal cysts that destroy the kidney. Mutations in PKD1 and PKD2, encoding polycystins-1 and -2, cause ADPKD. Polycystins are thought to function in primary cilia, but it is not well understood how these and other proteins are targete...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001361
更新日期:2011-04-01 00:00:00
abstract::The human nuclear poly(A)-binding protein PABPN1 has been implicated in the decay of nuclear noncoding RNAs (ncRNAs). In addition, PABPN1 promotes hyperadenylation by stimulating poly(A)-polymerases (PAPα/γ), but this activity has not previously been linked to the decay of endogenous transcripts. Moreover, the mechani...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005610
更新日期:2015-10-20 00:00:00
abstract::A critical problem in biology is understanding how cells choose between self-renewal and differentiation. To generate a comprehensive view of the mechanisms controlling early hematopoietic precursor self-renewal and differentiation, we used systems-based approaches and murine EML multipotential hematopoietic precursor...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002565
更新日期:2012-01-01 00:00:00
abstract::Human genome-wide association studies have linked single nucleotide polymorphisms (SNPs) on chromosome 9p21.3 near the INK4/ARF (CDKN2a/b) locus with susceptibility to atherosclerotic vascular disease (ASVD). Although this locus encodes three well-characterized tumor suppressors, p16(INK4a), p15(INK4b), and ARF, the S...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001233
更新日期:2010-12-02 00:00:00