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1.
Science ; 343(6166): 77-80, 2014 Jan 03.
Article in English | MEDLINE | ID: mdl-24385627

ABSTRACT

Metaphase chromosomes are visible hallmarks of mitosis, yet our understanding of their structure and of the forces shaping them is rudimentary. Phosphorylation of histone H3 serine 10 (H3 S10) by Aurora B kinase is a signature event of mitosis, but its function in chromatin condensation is unclear. Using genetically encoded ultraviolet light-inducible cross-linkers, we monitored protein-protein interactions with spatiotemporal resolution in living yeast to identify the molecular details of the pathway downstream of H3 S10 phosphorylation. This modification leads to the recruitment of the histone deacetylase Hst2p that subsequently removes an acetyl group from histone H4 lysine 16, freeing the H4 tail to interact with the surface of neighboring nucleosomes and promoting fiber condensation. This cascade of events provides a condensin-independent driving force of chromatin hypercondensation during mitosis.


Subject(s)
Chromatin/metabolism , Histones/metabolism , Mitosis , Protein Processing, Post-Translational , Saccharomyces cerevisiae/metabolism , Serine/metabolism , Adenosine Triphosphatases/metabolism , Chromosomes, Fungal/genetics , Chromosomes, Fungal/metabolism , Cross-Linking Reagents/chemistry , Cross-Linking Reagents/radiation effects , DNA-Binding Proteins/metabolism , Lysine/metabolism , Multiprotein Complexes/metabolism , Phosphorylation , Protein Interaction Mapping , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/metabolism , Sirtuin 2/metabolism
2.
Article in English | MEDLINE | ID: mdl-24032881

ABSTRACT

Conventionally, pairwise relationships between nodes are considered to be the fundamental building blocks of complex networks. However, over the last decade, the overabundance of certain subnetwork patterns, i.e., the so-called motifs, has attracted much attention. It has been hypothesized that these motifs, instead of links, serve as the building blocks of network structures. Although the relation between a network's topology and the general properties of the system, such as its function, its robustness against perturbations, or its efficiency in spreading information, is the central theme of network science, there is still a lack of sound generative models needed for testing the functional role of subgraph motifs. Our work aims to overcome this limitation. We employ the framework of exponential random graph models (ERGMs) to define models based on triadic substructures. The fact that only a small portion of triads can actually be set independently poses a challenge for the formulation of such models. To overcome this obstacle, we use Steiner triple systems (STSs). These are partitions of sets of nodes into pair-disjoint triads, which thus can be specified independently. Combining the concepts of ERGMs and STSs, we suggest generative models capable of generating ensembles of networks with nontrivial triadic Z-score profiles. Further, we discover inevitable correlations between the abundance of triad patterns, which occur solely for statistical reasons and need to be taken into account when discussing the functional implications of motif statistics. Moreover, we calculate the degree distributions of our triadic random graphs analytically.

3.
Phys Rev E Stat Nonlin Soft Matter Phys ; 86(1 Pt 2): 016203, 2012 Jul.
Article in English | MEDLINE | ID: mdl-23005503

ABSTRACT

Networks of chaotic units with static couplings can synchronize to a common chaotic trajectory. The effect of dynamic adaptive couplings on the cooperative behavior of chaotic networks is investigated. The couplings adjust to the activities of its two units by two competing mechanisms: An exponential decrease of the coupling strength is compensated for by an increase due to desynchronized activity. This mechanism prevents the network from reaching a steady state. Numerical simulations of a coupled map lattice show chaotic trajectories of desynchronized units interrupted by pulses of mutually synchronized clusters. These pulses occur on all scales, sometimes extending to the entire network. Clusters of synchronized units can be triggered by a small group of synchronized units.


Subject(s)
Feedback , Models, Theoretical , Nonlinear Dynamics , Oscillometry/methods , Computer Simulation
4.
Dev Genes Evol ; 219(8): 399-407, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19760181

ABSTRACT

The genetic control of leg development is well characterized in the fly Drosophila melanogaster. These control mechanisms, however, must differ to some degree between different insect species to account for the morphological diversity of thoracic legs in the insects. The legs of the flour beetle Tribolium castaneum differ from the Drosophila legs in their developmental mode as well as in their specific morphology especially at the larval stage. In order to identify genes involved in the morphogenesis of the Tribolium larval legs, we have analyzed EGFP enhancer trap lines of Tribolium. We have identified the zfh2 gene as a novel factor required for normal leg development in Tribolium. RNA interference with zfh2 function leads to two alternative classes of leg phenotype. The loss of a leg segment boundary and the generation of ectopic outgrowths in one class of phenotype suggest a role in leg segmentation and segment growth. The malformation of the pretarsal claw in the second class of phenotype suggests a role in distal development and the morphogenesis of the claw-shaped morphology of the pretarsus. This suggests that zfh2 is involved in the regulation of an unidentified target gene in a concentration-dependent manner. Our results demonstrate that enhancer trap screens in T. castaneum have the potential to identify novel gene functions regulating specific developmental processes.


Subject(s)
DNA-Binding Proteins/metabolism , Genes, Insect , Tribolium/growth & development , Tribolium/genetics , Animals , Body Patterning , DNA-Binding Proteins/genetics , Extremities/growth & development , Gene Expression Regulation, Developmental , Green Fluorescent Proteins/metabolism , Larva/growth & development , Mutagenesis, Insertional
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