A new strategy for isolating genes controlling dosage compensation in Drosophila using a simple epigenetic mosaic eye phenotype

<p>Abstract</p> <p>Background</p> <p>The <it>Drosophila </it>Male Specific Lethal (MSL) complex contains chromatin modifying enzymes and non-coding <it>roX </it>RNA. It paints the male X at hundreds of bands where it acetylates histone H4 at lysine 16. This epigenetic mark increases expression from the single male X chromosome approximately twofold above what gene-specific factors produce from each female X chromosome. This equalises X-linked gene expression between the sexes. Previous screens for components of dosage compensation relied on a distinctive male-specific lethal phenotype.</p> <p>Results</p> <p>Here, we report a new strategy relying upon an unusual male-specific mosaic eye pigmentation phenotype produced when the MSL complex acts upon autosomal <it>roX1 </it>transgenes. Screening the second chromosome identified at least five loci, two of which are previously described components of the MSL complex. We focused our analysis on the modifier alleles of MSL1 and MLE (for 'maleless'). The MSL1 lesions are not simple nulls, but rather alter the PEHE domain that recruits the MSL3 chromodomain and MOF ('males absent on first') histone acetyltransferase subunits to the complex. These mutants are compromised in their ability to recruit MSL3 and MOF, dosage compensate the X, and support long distance spreading from <it>roX1 </it>transgenes. Yet, paradoxically, they were isolated because they somehow increase MSL complex activity immediately around <it>roX1 </it>transgenes in combination with wild-type MSL1 subunits.</p> <p>Conclusions</p> <p>We propose that these diverse phenotypes arise from perturbations in assembly of MSL subunits onto nascent <it>roX </it>transcripts. This strategy is a promising alternative route for identifying previously unknown components of the dosage compensation pathway and novel alleles of known MSL proteins.</p

Progress and prospects toward our understanding of the evolution of dosage compensation

In many eukaryotic organisms, gender is determined by a pair of heteromorphic sex chromosomes. Degeneration of the non-recombining Y chromosome is a general facet of sex chromosome evolution. Selective pressure to restore expression levels of X-linked genes relative to autosomes accompanies Y-chromosome degeneration, thus driving the evolution of dosage compensation mechanisms. This review focuses on evolutionary aspects of dosage compensation, in light of recent advances in comparative and functional genomics that have substantially increased our understanding of the molecular mechanisms of dosage compensation and how it evolved. We review processes involved in sex chromosome evolution, and discuss the dynamic interaction between Y degeneration and the acquisition of dosage compensation. We compare mechanisms of dosage compensation and the origin of dosage compensation genes between different taxa and comment on sex chromosomes that apparently lack compensation mechanisms. Finally, we discuss how dosage compensation systems can also influence the evolution of well-established sex chromosomes

Evidence of Activity-Specific, Radial Organization of Mitotic Chromosomes in Drosophila

A fluorescently labeled protein specifically binding to genes was reproducibly found at the periphery of condensed mitotic fruit fly chromosomes, illustrating preservation of a radial structure between consecutive divisions

X chromosomal regulation in flies: when less is more

In Drosophila, dosage compensation of the single male X chromosome involves upregulation of expression of X linked genes. Dosage compensation complex or the male specific lethal (MSL) complex is intimately involved in this regulation. The MSL complex members decorate the male X chromosome by binding on hundreds of sites along the X chromosome. Recent genome wide analysis has brought new light into X chromosomal regulation. It is becoming increasingly clear that although the X chromosome achieves male specific regulation via the MSL complex members, a number of general factors also impinge on this regulation. Future studies integrating these aspects promise to shed more light into this epigenetic phenomenon

Xist regulation and function eXplored

X chromosome inactivation (XCI) is a process in mammals that ensures equal transcript levels between males and females by genetic inactivation of one of the two X chromosomes in females. Central to XCI is the long non-coding RNA Xist, which is highly and specifically expressed from the inactive X chromosome. Xist covers the X chromosome in cis and triggers genetic silencing, but its working mechanism remains elusive. Here, we review current knowledge about Xist regulation, structure, function and conservation and speculate on possible mechanisms by which its action is restricted in cis. We also discuss dosage compensation mechanisms other than XCI and how knowledge from invertebrate species may help to provide a better understanding of the mechanisms of mammalian XCI

Inventory routing in a warehouse: The storage replenishment routing problem

In warehouses, storage replenishment operations involve the transportation of items to capacitated item slots in the forward storage area from reserve storage. These items are later picked from these slots as demand arises. While order picking constitutes the majority of warehouse operating costs, efficient management of replenishment operations is important to ensure the availability of the items for picking and to decrease the operating costs due to replenishment, which might be particularly higher in warehouses with fast-moving items (e.g., e-commerce warehouses or retail distribution centers). In this paper, we define the storage replenishment routing problem in a parallel-aisle warehouse, where replenishment and order picking operations are carried out in successive cycles with time limits. The aim is to determine the item slots that will be replenished and the route of the replenishment worker in each replenishment cycle, so as to minimize the total travel time and ensure the availability of items at the start of the cycle they will be picked. We present complexity results on different variants of the problem and show that the problem is -hard in general. Consequently, we adapt a heuristic approach based on a priori routing and inspired by the literature on the inventory routing problem. We use randomly generated warehouse instances to analyze the effects of different a priori routing methods and demand skewness patterns on replenishment performance, and to compare the proposed approach to benchmarks that mimic practice

Shelf Life of Polyamide 12 (PA2200) Laser Sintering Powder

It is a very well-known fact that polyamide powders age during processing in laser sintering. Therefore, the recycling rate of used powder is typically limited to around 50 % and it has to be mixed with new, virgin powder, before the next build job can be started. The aging of the polymer powder between its production and processing, in contrast, has hardly been investigated so far and has received little attention. In order to investigate the effects of storage time, optical, thermal and rheological tests were carried out on two batches of PA2200 powder, which had been stored for 5.5 and 6.5 years respectively. Compared to freshly produced powders, aging effects were clearly visible.Mechanical Engineerin