Numerous studies have shown that following retrieval, a previously consolidated memory requires increased transcriptional regulation in order to be reconsolidated. Previously, it was reported that histone H3 lysine-4 trimethylation (H3K4me3), a marker of active transcription, is increased in the hippocampus after the retrieval of contextual fear memory. However, it is currently unknown how this epigenetic mark is regulated during the reconsolidation process. Furthermore, though recent evidence suggests that neuronal activity triggers DNA double-strand breaks (DSBs) in some early-response genes, it is currently unknown if DSBs contribute to the reconsolidation of a memory following retrieval. Here, using chromatin immunoprecipitation (ChIP) analyses, we report a significant overlap between DSBs and H3K4me3 in area CA1 of the hippocampus during the reconsolidation process. We found an increase in phosphorylation of histone H2A.X at serine 139 (H2A.XpS139), a marker of DSB, in the Npas4, but not c-fos, promoter region 5 min after retrieval, which correlated with increased H3K4me3 levels, suggesting that the two epigenetic marks may work in concert during the reconsolidation process. Consistent with this, in vivo siRNA-mediated knockdown of topoisomerase II β, the enzyme responsible for DSB, prior to retrieval, reduced Npas4 promoter-specific H2A.XpS139 and H3K4me3 levels and impaired long-term memory, indicating an indispensable role of DSBs in the memory reconsolidation process. Collectively, our data propose a novel mechanism for memory reconsolidation through increases in epigenetic-mediated transcriptional control via DNA double-strand breaks.

The mitotic checkpoint (also called spindle assembly checkpoint, SAC) is a signaling pathway that safeguards proper chromosome segregation. Correct functioning of the SAC depends on adequate protein concentrations and appropriate stoichiometries between SAC proteins. Yet very little is known about the regulation of SAC gene expression. Here, we show in the fission yeast Schizosaccharomyces pombe that a combination of short mRNA half-lives and long protein half-lives supports stable SAC protein levels. For the SAC genes mad2 + and mad3 + , their short mRNA half-lives are caused, in part, by a high frequency of nonoptimal codons. In contrast, mad1 + mRNA has a short half-life despite a higher frequency of optimal codons, and despite the lack of known RNAdestabilizing motifs. Hence, different SAC genes employ different strategies of expression. We further show that Mad1 homodimers form co-translationally, which may necessitate a certain codon usage pattern. Taken together, we propose that the codon usage of SAC genes is fine-tuned to ensure proper SAC function. Our work shines light on gene expression features that promote spindle assembly checkpoint function and suggests that synonymous mutations may weaken the checkpoint.

VT Stories, an oral history research project with an interactive, Web-based delivery platform, was designed from initial concept through development to serve multiple purposes and to provide various audiences with a high level of digital engagement. Comprised of a collaborative group of Virginia Tech faculty, staff, and students from multiple disciplines, the VT Stories team collects, analyzes, and shares oral history interviews for several purposes. This article details how these oral histories are fashioned for digital and social media use, incorporated into the university library's Special Collections, and made available for multiple research purposes. The standalone website, linked to the university library's Special Collections Online, is a unique archive that both contributes to the public face of the institution's history and at the same time functions as a repository for exploring multiple avenues of research. The article highlights how an oral history project differs when explicitly designed with such digital end use in mind. We also discuss the hands-on experiences of students as they take related classes, work as website developers, interview as oral historians, and manage the project from story concept to published Web content.