Epigenomics and the structure of the living genome

Eukaryotic genomes are packaged into an extensively folded state known as chromatin. Analysis of the structure of eukaryotic chromosomes has been revolutionized by development of a suite of genome-wide measurement technologies, collectively termed epigenomics. We review major advances in epigenomic analysis of eukaryotic genomes, covering aspects of genome folding at scales ranging from whole chromosome folding down to nucleotide-resolution assays that provide structural insights into protein-DNA interactions. We then briefly outline several challenges remaining and highlight new developments such as single-cell epigenomic assays that will help provide us with a high-resolution structural understanding of eukaryotic genomes

Father-Son Chats: Inheriting Stress through Sperm RNA

Although mounting evidence in mammals suggests that certain ancestral environmental exposures can influence the phenotype in future generations, mechanisms underlying such intergenerational information transfer remain unclear. A recent report suggests that RNA isolated from sperm can inform offspring of a father’s history of early life trauma (Gapp et al., 2014)

Chromatin \u27programming\u27 by sequence - is there more to the nucleosome code than %GC

The role of genomic sequence in directing the packaging of eukaryotic genomes into chromatin has been the subject of considerable recent debate. A new paper from Tillo and Hughes shows that the intrinsic thermodynamic preference of a given sequence in the yeast genome for the histone octamer can largely be captured with a simple model, and in fact is mostly explained by %GC. Thus, the rules for predicting nucleosome occupancy from genomic sequence are much less complicated than has been claimed

Comparative Genomics Reveals Chd1 as a Determinant of Nucleosome Spacing in Vivo

Packaging of genomic DNA into nucleosomes is nearly universally conserved in eukaryotes, and many features of the nucleosome landscape are quite conserved. Nonetheless, quantitative aspects of nucleosome packaging differ between species because, for example, the average length of linker DNA between nucleosomes can differ significantly even between closely related species. We recently showed that the difference in nucleosome spacing between two Hemiascomycete species-Saccharomyces cerevisiae and Kluyveromyces lactis-is established by trans-acting factors rather than being encoded in cis in the DNA sequence. Here, we generated several S. cerevisiae strains in which endogenous copies of candidate nucleosome spacing factors are deleted and replaced with the orthologous factors from K. lactis. We find no change in nucleosome spacing in such strains in which H1 or Isw1 complexes are swapped. In contrast, the K. lactis gene encoding the ATP-dependent remodeler Chd1 was found to direct longer internucleosomal spacing in S. cerevisiae, establishing that this remodeler is partially responsible for the relatively long internucleosomal spacing observed in K. lactis. By analyzing several chimeric proteins, we find that sequence differences that contribute to the spacing activity of this remodeler are dispersed throughout the coding sequence, but that the strongest spacing effect is linked to the understudied N-terminal end of Chd1. Taken together, our data find a role for sequence evolution of a chromatin remodeler in establishing quantitative aspects of the chromatin landscape in a species-specific manner

First results of a cryogenic optical photon counting imaging spectrometer using a DROID array

Context. In this paper we present the first system test in which we demonstrate the concept of using an array of Distributed Read Out Imaging Devices (DROIDs) for optical photon detection. Aims. After the successful S-Cam 3 detector the next step in the development of a cryogenic optical photon counting imaging spectrometer under the S-Cam project is to increase the field of view using DROIDs. With this modification the field of view of the camera has been increased by a factor of 5 in area, while keeping the number of readout channels the same. Methods. The test has been performed using the flexible S-Cam 3 system and exchanging the 10x12 Superconducting Tunnel Junction array for a 3x20 DROID array. The extra data reduction needed with DROIDs is performed offline. Results. We show that, although the responsivity (number of tunnelled quasiparticles per unit of absorbed photon energy, e- /eV) of the current array is too low for direct astronomical applications, the imaging quality is already good enough for pattern detection, and will improve further with increasing responsivity. Conclusions. The obtained knowledge can be used to optimise the system for the use of DROIDs.Comment: 7 pages, 9 figures, accepted for publicaiton in A&

Early life lessons: The lasting effects of germline epigenetic information on organismal development

BACKGROUND: An organism\u27s metabolic phenotype is primarily affected by its genotype, its lifestyle, and the nutritional composition of its food supply. In addition, it is now clear from studies in many different species that ancestral environments can also modulate metabolism in at least one to two generations of offspring. SCOPE OF REVIEW: We limit ourselves here to paternal effects in mammals, primarily focusing on studies performed in inbred rodent models. Although hundreds of studies link paternal diets and offspring metabolism, the mechanistic basis by which epigenetic information in sperm programs nutrient handling in the next generation remains mysterious. Our goal in this review is to provide a brief overview of paternal effect paradigms and the germline epigenome. We then pivot to exploring one key mystery in this literature: how do epigenetic changes in sperm, most of which are likely to act transiently in the early embryo, ultimately direct a long-lasting physiological response in offspring? MAJOR CONCLUSIONS: Several potential mechanisms exist by which transient epigenetic modifications, such as small RNAs or methylation states erased shortly after fertilization, could be transferred to more durable heritable information. A detailed mechanistic understanding of this process will provide deep insights into early development, and could be of great relevance for human health and disease

Exploring public perceptions of creating and using 3D printed human remains

3D printed human remains offer an alternative presentation format to traditional photographs, that could be more effective and less emotive. However, the perception of the public regarding key questions, such as the use, ownership, and disposal of 3D printed remains in courts of law has not yet been established. This study explored whether the creation of 3D printed human remains could be considered as an ethical practice by members of the public. A survey comprised of 36 questions was designed to gather responses from members of the public (n = 400) about their attitudes to the creation and use of 3D printed human remains. A majority of respondents believed it was ethical to use 3D prints in courtroom demonstrations (more than 90%) and that this may help jurors to better understand expert testimony over photographs. Respondents also indicated that the context of the case and whether consent had been received from next of kin were important considerations. The results of this study indicate that there is a recognition that there is a direct connection between 3D printed remains and the individual from whom a print derives, and that there is a clear public interest in ensuring that prints are used ethically and responsibly. Yet there are currently no guidelines for what constitutes best ethical practice for the creation and utilisation of 3D prints. As we look forward, there is a need to identify how best to treat 3D printed remains with dignity and respect in casework in a manner that is also contextually appropriate