Clavis Aurea : An Augmented Reality Game for the Teaching of Local History

The aim of this study was the design, development, and evaluation of an Augmented Reality game to teach students about the local history of a Greek island. Design-based research served as the foundation of this study’s methodology. Experts in ICT in education, teachers with knowledge of the local history and primary education students participated in the evaluation of this study. The results of the evaluation showed that the game presents satisfactory levels of usability and that its content is compatible with the island’s local history. Among the factors influencing its use by students were internet connectivity, the large number of visitors at the archaeological site where the game was played, and the problem of coordinating the student groups

Transcriptional loops meet chromatin: a dual-layer network controls white–opaque switching in Candida albicans

The human pathogen Candida albicans is able to undergo a reversible switch between two distinct cell types called white and opaque, which are considered different transcriptional states of cells harbouring identical genomes. The present model of switching regulation includes the bistable expression of a master switch gene that is controlled by multiple transcriptional feedback loops. Here, we show that chromatin-modifying enzymes constitute an additional important regulatory layer of morphogenetic switching. We identify eight chromatin modifiers as switching modulators. Extensive epistasis analysis maps them into at least two independent signalling pathways overlaying the known transcriptional network. Interestingly, we identify the conserved Set3/Hos2 histone deacetylase complex as a key regulator relying on the methylation status of histone H3 lysine 4 for switching modulation. Furthermore, we demonstrate that opaque to white switching is facilitated by the presence of adenine in vitro, but adenine has no effect on switching once the Set3/Hos2 complex is disrupted. Our observations postulate that chromatin modifications may serve as a means to integrate environmental or host stimuli through the underlying transcriptional circuits to determine cell fate in C. albicans

ASH1, a Drosophila trithorax group protein, is required for methylation of lysine 4 residues on histone H3

Covalent modifications of histone tails modulate gene expression via chromatin organization. As examples, methylation of lysine 9 residues of histone H3 (H3) (H3-K9) is believed to repress transcription by compacting chromatin, whereas methylation of lysine 4 residues of H3 (H3-K4) is believed to activate transcription by relaxing chromatin. The Drosophila trithorax group protein absent, small, or homeotic discs 1 (ASH1) is involved in maintaining active transcription of many genes. Here we report that in extreme ash1 mutants, no H3-K4 methylation is detectable. Within the limits of our assays, this lack of detectable H3-K4 methylation implies that ASH1 is required for essentially all H3-K4 methylation that occurs in vivo. We report further that the 149-aa SET domain of ASH1 is sufficient for H3-K4 methylation in vitro. These findings support a model in which ASH1 is directly involved in maintaining active transcription by conferring a relaxed chromatin structure

Crystal Structure of the Human Histone Methyltransferase ASH1L Catalytic Domain and Its Implications for the Regulatory Mechanism*

Absent, small, or homeotic disc1 (Ash1) is a trithorax group histone methyltransferase that is involved in gene activation. Although there are many known histone methyltransferases, their regulatory mechanisms are poorly understood. Here, we present the crystal structure of the human ASH1L catalytic domain, showing its substrate binding pocket blocked by a loop from the post-SET domain. In this configuration, the loop limits substrate access to the active site. Mutagenesis of the loop stimulates ASH1L histone methyltransferase activity, suggesting that ASH1L activity may be regulated through the loop from the post-SET domain. In addition, we show that human ASH1L specifically methylates histone H3 Lys-36. Our data implicate that there may be a regulatory mechanism of ASH1L histone methyltransferases