Broad Chromatin Domains: An Important Facet of Genome Regulation.

Chromatin composition differs across the genome, with distinct compositions characterizing regions associated with different properties and functions. Whereas many histone modifications show local enrichment over genes or regulatory elements, marking can also span large genomic intervals defining broad chromatin domains. Here we highlight structural and functional features of chromatin domains marked by histone modifications, with a particular emphasis on the potential roles of H3K27 methylation domains in the organization and regulation of genome activity in metazoans

The histone binding capacity of SPT2 controls chromatin structure and function in Metazoa

Histone chaperones control nucleosome density and chromatin structure. In yeast, the H3-H4 chaperone Spt2 controls histone deposition at active genes but its roles in metazoan chromatin structure and organismal physiology are not known. Here we identify the Caenorhabditis elegans ortholog of SPT2 (CeSPT-2) and show that its ability to bind histones H3-H4 is important for germline development and transgenerational epigenetic gene silencing, and that spt-2 null mutants display signatures of a global stress response. Genome-wide profiling showed that CeSPT-2 binds to a range of highly expressed genes, and we find that spt-2 mutants have increased chromatin accessibility at a subset of these loci. We also show that SPT2 influences chromatin structure and controls the levels of soluble and chromatin-bound H3.3 in human cells. Our work reveals roles for SPT2 in controlling chromatin structure and function in Metazoa.</p

Mitochondrial Diabetes in Children: Seek and You Will Find It

Maternally Inherited Diabetes and Deafness (MIDD) is a rare form of diabetes due to defects in mitochondrial DNA (mtDNA). 3243 A>G is the mutation most frequently associated with this condition, but other mtDNA variants have been linked with a diabetic phenotype suggestive of MIDD. From 1989 to 2009, we clinically diagnosed mitochondrial diabetes in 11 diabetic children. Diagnosis was based on the presence of one or more of the following criteria: 1) maculopathy; 2) hearing impairment; 3) maternal heritability of diabetes/impaired fasting glucose and/or hearing impairment and/or maculopathy in three consecutive generations (or in two generations if 2 or 3 members of a family were affected). We sequenced the mtDNA in the 11 probands, in their mothers and in 80 controls. We identified 33 diabetes-suspected mutations, 1/33 was 3243A>G. Most patients (91%) and their mothers had mutations in complex I and/or IV of the respiratory chain. We measured the activity of these two enzymes and found that they were less active in mutated patients and their mothers than in the healthy control pool. The prevalence of hearing loss (36% vs 75–98%) and macular dystrophy (54% vs 86%) was lower in our mitochondrial diabetic adolescents than reported in adults. Moreover, we found a hitherto unknown association between mitochondrial diabetes and celiac disease. In conclusion, mitochondrial diabetes should be considered a complex syndrome with several phenotypic variants. Moreover, deafness is not an essential component of the disease in children. The whole mtDNA should be screened because the 3243A>G variant is not as frequent in children as in adults. In fact, 91% of our patients were mutated in the complex I and/or IV genes. The enzymatic assay may be a useful tool with which to confirm the pathogenic significance of detected variants

Analysis of high-identity segmental duplications in the grapevine genome

<p>Abstract</p> <p>Background</p> <p>Segmental duplications (SDs) are blocks of genomic sequence of 1-200 kb that map to different loci in a genome and share a sequence identity > 90%. SDs show at the sequence level the same characteristics as other regions of the human genome: they contain both high-copy repeats and gene sequences. SDs play an important role in genome plasticity by creating new genes and modeling genome structure. Although data is plentiful for mammals, not much was known about the representation of SDs in plant genomes. In this regard, we performed a genome-wide analysis of high-identity SDs on the sequenced grapevine (<it>Vitis vinifera</it>) genome (PN40024).</p> <p>Results</p> <p>We demonstrate that recent SDs (> 94% identity and >= 10 kb in size) are a relevant component of the grapevine genome (85 Mb, 17% of the genome sequence). We detected mitochondrial and plastid DNA and genes (10% of gene annotation) in segmentally duplicated regions of the nuclear genome. In particular, the nine highest copy number genes have a copy in either or both organelle genomes. Further we showed that several duplicated genes take part in the biosynthesis of compounds involved in plant response to environmental stress.</p> <p>Conclusions</p> <p>These data show the great influence of SDs and organelle DNA transfers in modeling the <it>Vitis vinifera </it>nuclear DNA structure as well as the impact of SDs in contributing to the adaptive capacity of grapevine and the nutritional content of grape products through genome variation. This study represents a step forward in the full characterization of duplicated genes important for grapevine cultural needs and human health.</p

Strain sensors based on Fiber Bragg Gratings for volcano monitoring

We present the experimental activity on the development of a Fiber Bragg Grating (FBG) strain sensor for volcano monitoring. We produced and tested a prototype of FBG strain sensor, with a high resolution and accuracy in static measurements and with a low-cost readout system. Here we present the results of a field campaign with a preliminary single-axis FBG strain sensor prototype on Mt. Etna, which was carried out in order to check the system performances in out-of-the-lab conditions and in the hostile volcanic environment (lack of mains electricity for power, strong diurnal temperature changes, strong wind, erosive ash, snow and ice during the winter time), and to determine whether measurable changes are induced across a 1989 fracture system during the paroxysmal phases of Etna's volcanic activity. In addition we present the design and laboratory test of a multi-axis strain sensor configuration

The histone chaperone SPT2 regulates chromatin structure and function in Metazoa.

Acknowledgements: We are grateful to members of the Labib laboratory for invaluable advice on recombinant protein purification and C. elegans techniques, and to members of the Rouse laboratory for fruitful discussion. We thank K. Rasmussen for help with ATAC–seq in human cells; R. Sundaramoorthy and T. Owen-Hughes (University of Dundee) for the gift of recombinant Xenopus histones; B. Meier and F. Pelisch for help with C. elegans genetics; K. Labib for helpful comments on the manuscript and for the gift of the His6–Ulp1 plasmid; V. Alvarez for help with microscopy and A. Knebel for advice on protein purification. We thank the technical support of the MRC PPU including the DNA Sequencing Service, Tissue Culture team, Reagents and Services team, and the Flow Cytometry & Cell Sorting Facility at the University of Dundee; we thank the (EPI)2 Imaging platform - UMR7216 Epigenetics and Cell Fate centre (Paris) for access to instruments; we also thank N. Wood for help with cloning, and F. Brown and J. Hastie for SPT2 antibody production and purification. We acknowledge the excellent support teams and admin staff in MRC PPU and the School of Life Sciences (University of Dundee) where most of this work was done. This work was supported by the Medical Research Council (grant number MC_UU_00018/5) and the pharmaceutical companies supporting the Division of Signal Transduction Therapy Unit (Boehinger‐Ingelheim, GlaxoSmithKline and Merck KGaA) (J.R.); the Wellcome Trust (grant number 217170) and the MRC (grant number MR/S021620/1) (J.A.); the Korean Institute for Basic Science (grant number IBS-R022-A2-2023) (A.G. and S.G.M.R.); Cancer Research UK (grant number C13474/A27826) and the Wellcome Trust (grant number 219475/Z/19/Z) (E.A.M.); the European Research Council (grant number ERC-2018-CoG-818625) (S.E.P.); the Medical Research Council (grant number MC_UU_00007/15) (C.P.P.); the European Research Council (ERC-2016-StG-715127) (C.A.); the Medical Research Council (grant number MC_U105192715 to L. Passmore). G.S. was supported by an EMBO Long-Term Fellowship (ALTF 951-2018) and a SULSA ECR Development Fund; this project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 845448 (G.S.). G.F. was supported by an EMBO Long-Term Fellowship (ALTF 1132-2018). P.A. was supported by an EMBO Long-Term Fellowship (ALTF 692–2018). For the purpose of open access, the MRC Protein Phosphorylation and Ubiquitylation Unit has applied a CC BY public copyright license to any Author Accepted Manuscript version arising. The funders had no direct role in study design, data collection and analysis, decision to publish or preparation of the manuscript.Histone chaperones control nucleosome density and chromatin structure. In yeast, the H3-H4 chaperone Spt2 controls histone deposition at active genes but its roles in metazoan chromatin structure and organismal physiology are not known. Here we identify the Caenorhabditis elegans ortholog of SPT2 (CeSPT-2) and show that its ability to bind histones H3-H4 is important for germline development and transgenerational epigenetic gene silencing, and that spt-2 null mutants display signatures of a global stress response. Genome-wide profiling showed that CeSPT-2 binds to a range of highly expressed genes, and we find that spt-2 mutants have increased chromatin accessibility at a subset of these loci. We also show that SPT2 influences chromatin structure and controls the levels of soluble and chromatin-bound H3.3 in human cells. Our work reveals roles for SPT2 in controlling chromatin structure and function in Metazoa

Exploring a dynamical path for C2H− and NCO− formation in dark molecular clouds

This paper deals with the possible formation of two molecular anions often considered likely components in the physical environments of the interstellar medium (ISM): C2H− and NCO−. They are both discussed here by computationally following the radiative association (RA) mechanism starting from C2−, H, N− and O as partners. The corresponding RA total cross sections produced by the calculations are in turn employed to generate the overall association rates over the relevant range of temperatures. The latter are found to be in line with other molecular ions formed by RA but not large enough to uniquivocally suggest this path as the main route to the anions formation in the ISM. Other possible paths of formation are also analysed and discussed. The presence of resonant structures during the association dynamics for both systems is found by the calculations and their consequences are discussed in some detail in the present study