Multifactorial Regulation of a Hox Target Gene

Hox proteins play fundamental roles in controlling morphogenetic diversity along the anterior–posterior body axis of animals by regulating distinct sets of target genes. Within their rather broad expression domains, individual Hox proteins control cell diversification and pattern formation and consequently target gene expression in a highly localized manner, sometimes even only in a single cell. To achieve this high-regulatory specificity, it has been postulated that Hox proteins co-operate with other transcription factors to activate or repress their target genes in a highly context-specific manner in vivo. However, only a few of these factors have been identified. Here, we analyze the regulation of the cell death gene reaper (rpr) by the Hox protein Deformed (Dfd) and suggest that local activation of rpr expression in the anterior part of the maxillary segment is achieved through a combinatorial interaction of Dfd with at least eight functionally diverse transcriptional regulators on a minimal enhancer. It follows that context-dependent combinations of Hox proteins and other transcription factors on small, modular Hox response elements (HREs) could be responsible for the proper spatio-temporal expression of Hox targets. Thus, a large number of transcription factors are likely to be directly involved in Hox target gene regulation in vivo

Genetic architecture of nonadditive inheritance in Arabidopsis thaliana hybrids

The ubiquity of nonparental hybrid phenotypes, such as hybrid vigor and hybrid inferiority, has interested biologists for over a century and is of considerable agricultural importance. Although examples of both phenomena have been subject to intense investigation, no general model for the molecular basis of nonadditive genetic variance has emerged, and prediction of hybrid phenotypes from parental information continues to be a challenge. Here we explore the genetics of hybrid phenotype in 435 Arabidopsis thaliana individuals derived from intercrosses of 30 parents in a half diallel mating scheme. We find that nonadditive genetic effects are a major component of genetic variation in this population and that the genetic basis of hybrid phenotype can be mapped using genome-wide association (GWA) techniques. Significant loci together can explain as much as 20% of phenotypic variation in the surveyed population and include examples that have both classical dominant and overdominant effects. One candidate region inherited dominantly in the half diallel contains the gene for the MADS-box transcription factor AGAMOUS-LIKE 50 (AGL50), which we show directly to alter flowering time in the predicted manner. Our study not only illustrates the promise of GWA approaches to dissect the genetic architecture underpinning hybrid performance but also demonstrates the contribution of classical dominance to genetic variance

Species-wide Genetic Incompatibility Analysis Identifies Immune Genes as Hot Spots of Deleterious Epistasis

SummaryIntraspecific genetic incompatibilities prevent the assembly of specific alleles into single genotypes and influence genome- and species-wide patterns of sequence variation. A common incompatibility in plants is hybrid necrosis, characterized by autoimmune responses due to epistatic interactions between natural genetic variants. By systematically testing thousands of F1 hybrids of Arabidopsis thaliana strains, we identified a small number of incompatibility hot spots in the genome, often in regions densely populated by nucleotide-binding domain and leucine-rich repeat (NLR) immune receptor genes. In several cases, these immune receptor loci interact with each other, suggestive of conflict within the immune system. A particularly dangerous locus is a highly variable cluster of NLR genes, DM2, which causes multiple independent incompatibilities with genes that encode a range of biochemical functions, including NLRs. Our findings suggest that deleterious interactions of immune receptors limit the combinations of favorable disease resistance alleles accessible to plant genomes

Species-wide genetic incompatibility analysis identifies immune genes as hot spots of deleterious epistasis

Intraspecific genetic incompatibilities prevent the assembly of specific alleles into single genotypes and influence genome- and species-wide patterns of sequence variation. A common incompatibility in plants is hybrid necrosis, characterized by autoimmune responses due to epistatic interactions between natural genetic variants. By systematically testing thousands of F1 hybrids of Arabidopsis thaliana strains, we identified a small number of incompatibility hot spots in the genome, often in regions densely populated by nucleotide-binding domain and leucine-rich repeat (NLR) immune receptor genes. In several cases, these immune receptor loci interact with each other, suggestive of conflict within the immune system. A particularly dangerous locus is a highly variable cluster of NLR genes, DM2, which causes multiple independent incompatibilities with genes that encode a range of biochemical functions, including NLRs. Our findings suggest that deleterious interactions of immune receptors limit the combinations of favorable disease resistance alleles accessible to plant genomes. © 2014 Elsevier In

The ATLAS experiment at the CERN Large Hadron Collider: a description of the detector configuration for Run 3

Abstract The ATLAS detector is installed in its experimental cavern at Point 1 of the CERN Large Hadron Collider. During Run 2 of the LHC, a luminosity of  ℒ = 2 × 1034 cm-2 s-1 was routinely achieved at the start of fills, twice the design luminosity. For Run 3, accelerator improvements, notably luminosity levelling, allow sustained running at an instantaneous luminosity of  ℒ = 2 × 1034 cm-2 s-1, with an average of up to 60 interactions per bunch crossing. The ATLAS detector has been upgraded to recover Run 1 single-lepton trigger thresholds while operating comfortably under Run 3 sustained pileup conditions. A fourth pixel layer 3.3 cm from the beam axis was added before Run 2 to improve vertex reconstruction and b-tagging performance. New Liquid Argon Calorimeter digital trigger electronics, with corresponding upgrades to the Trigger and Data Acquisition system, take advantage of a factor of 10 finer granularity to improve triggering on electrons, photons, taus, and hadronic signatures through increased pileup rejection. The inner muon endcap wheels were replaced by New Small Wheels with Micromegas and small-strip Thin Gap Chamber detectors, providing both precision tracking and Level-1 Muon trigger functionality. Trigger coverage of the inner barrel muon layer near one endcap region was augmented with modules integrating new thin-gap resistive plate chambers and smaller-diameter drift-tube chambers. Tile Calorimeter scintillation counters were added to improve electron energy resolution and background rejection. Upgrades to Minimum Bias Trigger Scintillators and Forward Detectors improve luminosity monitoring and enable total proton-proton cross section, diffractive physics, and heavy ion measurements. These upgrades are all compatible with operation in the much harsher environment anticipated after the High-Luminosity upgrade of the LHC and are the first steps towards preparing ATLAS for the High-Luminosity upgrade of the LHC. This paper describes the Run 3 configuration of the ATLAS detector.</jats:p

The ATLAS experiment at the CERN Large Hadron Collider: a description of the detector configuration for Run 3

Abstract The ATLAS detector is installed in its experimental cavern at Point 1 of the CERN Large Hadron Collider. During Run 2 of the LHC, a luminosity of  ℒ = 2 × 1034 cm-2 s-1 was routinely achieved at the start of fills, twice the design luminosity. For Run 3, accelerator improvements, notably luminosity levelling, allow sustained running at an instantaneous luminosity of  ℒ = 2 × 1034 cm-2 s-1, with an average of up to 60 interactions per bunch crossing. The ATLAS detector has been upgraded to recover Run 1 single-lepton trigger thresholds while operating comfortably under Run 3 sustained pileup conditions. A fourth pixel layer 3.3 cm from the beam axis was added before Run 2 to improve vertex reconstruction and b-tagging performance. New Liquid Argon Calorimeter digital trigger electronics, with corresponding upgrades to the Trigger and Data Acquisition system, take advantage of a factor of 10 finer granularity to improve triggering on electrons, photons, taus, and hadronic signatures through increased pileup rejection. The inner muon endcap wheels were replaced by New Small Wheels with Micromegas and small-strip Thin Gap Chamber detectors, providing both precision tracking and Level-1 Muon trigger functionality. Trigger coverage of the inner barrel muon layer near one endcap region was augmented with modules integrating new thin-gap resistive plate chambers and smaller-diameter drift-tube chambers. Tile Calorimeter scintillation counters were added to improve electron energy resolution and background rejection. Upgrades to Minimum Bias Trigger Scintillators and Forward Detectors improve luminosity monitoring and enable total proton-proton cross section, diffractive physics, and heavy ion measurements. These upgrades are all compatible with operation in the much harsher environment anticipated after the High-Luminosity upgrade of the LHC and are the first steps towards preparing ATLAS for the High-Luminosity upgrade of the LHC. This paper describes the Run 3 configuration of the ATLAS detector.</jats:p