Lysine 27 dimethylation of Drosophila linker histone dH1 contributes to heterochromatin organization independently of H3K9 methylation

Post-translational modifications (PTMs) of core histones are important epigenetic determinants that correlate with functional chromatin states. However, despite multiple linker histone H1s PTMs have been identified, little is known about their genomic distribution and contribution to the epigenetic regulation of chromatin. Here, we address this question in Drosophila that encodes a single somatic linker histone, dH1. We previously reported that dH1 is dimethylated at K27 (dH1K27me2). Here, we show that dH1K27me2 is a major PTM of Drosophila heterochromatin. At mitosis, dH1K27me2 accumulates at pericentromeric heterochromatin, while, in interphase, it is also detected at intercalary heterochromatin. ChIPseq experiments show that >98% of dH1K27me2 enriched regions map to heterochromatic repetitive DNA elements, including transposable elements, simple DNA repeats and satellite DNAs. Moreover, expression of a mutated dH1K27A form, which impairs dH1K27me2, alters heterochromatin organization, upregulates expression of heterochromatic transposable elements and results in the accumulation of RNA:DNA hybrids (R-loops) in heterochromatin, without affecting H3K9 methylation and HP1a binding. The pattern of dH1K27me2 is H3K9 methylation independent, as it is equally detected in flies carrying a H3K9R mutation, and is not affected by depletion of Su(var)3–9, HP1a or Su(var)4–20. Altogether these results suggest that dH1K27me2 contributes to heterochromatin organization independently of H3K9 methylation.MICIN/AEI 10.13039/501100011033 [BFU2015-65082-P and PGC2018-094538-B-100]; ‘FEDER, una manera de hacer Europa’; Generalitat de Catalunya [SGR2014-204, SGR2017-475]; this work was carried out within the framework of the ‘Centre de Referencia en Biotecnologia’ of ` the Generalitat de Catalunya. Funding for open access charge: MINECO [PGC2018-094538-B-100]. Conflict of interest statement. None declared

3D Technologies to Acquire and Visualize the Human Body for Improving Dietetic Treatment

This research aims to improve adherence to dietetic-nutritional treatment using state-of-the-art RGB-D sensor and virtual reality (VR) technology. Recent studies show that adherence to treatment can be improved by using multimedia technologies which impact on the body awareness of patients. However, there are no studies published to date using 3D data and VR technologies for this purpose. This paper describes a system capable of obtaining the complete 3D model of a body with high accuracy and a realistic visualization for 2D and VR devices to be used for studying the effect of 3D technologies on adherence to obesity treatment.This work has been partially funded by the Spanish Government TIN2017-89069-R grant supported with Feder funds

A high-resolution spatial assessment of the impacts of drought variability on vegetation activity in Spain from 1981 to 2015

59 Pags.- 12 Tabls.- 35 Figs. © Author(s) 2019. This work is distributed under the Creative Commons Attribution 4.0 License.Drought is a major driver of vegetation activity in Spain, with significant impacts on crop yield, forest growth, and the occurrence of forest fires. Nonetheless, the sensitivity of vegetation to drought conditions differs largely amongst vegetation types and climates. We used a high-resolution (1.1 km) spatial dataset of the normalized difference vegetation index (NDVI) for the whole of Spain spanning the period from 1981 to 2015, combined with a dataset of the standardized precipitation evapotranspiration index (SPEI) to assess the sensitivity of vegetation types to drought across Spain. Specifically, this study explores the drought timescales at which vegetation activity shows its highest response to drought severity at different moments of the year. Results demonstrate that – over large areas of Spain – vegetation activity is controlled largely by the interannual variability of drought. More than 90 % of the land areas exhibited statistically significant positive correlations between the NDVI and the SPEI during dry summers (JJA). Nevertheless, there are some considerable spatio-temporal variations, which can be linked to differences in land cover and aridity conditions. In comparison to other climatic regions across Spain, results indicate that vegetation types located in arid regions showed the strongest response to drought. Importantly, this study stresses that the timescale at which drought is assessed is a dominant factor in understanding the different responses of vegetation activity to drought.This research has been supported by the Spanish Commission of Science and Technology and FEDER (grant no. PCIN-2015-220), the Spanish Commission of Science and Technology and FEDER (grant no. CGL2014-52135-C03-01), the Spanish Commission of Science and Technology and FEDER (grant no. CGL2017-83866-C3-3-R), the Spanish Commission of Science and Technology and FEDER (grant no. CGL2017-82216-R), WaterWorks 2014 (grant no. 690462, IMDROFLOOD), the JPI Climate (grant no. 690462, INDECIS), and WaterWorks 2015 (FORWARD grant).Peer reviewe

Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the mediterranean diet pattern is low

BACKGROUND: Although the fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet). METHODS: Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic subjects) with no differences in BMI. Diet was assessed by validated questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate genetic score was calculated to test additive effects. Gene-diet interactions were analyzed. RESULTS: Neither of the polymorphisms was associated with type 2 diabetes in the whole population. However, we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO-rs9939609 (P-interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their aggregate score (P-interaction=0.006). When adherence to the MedDiet was low, carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO-rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO-rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These gene-diet interactions remained significant even after adjustment for BMI. As MedDiet is rich in folate, we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose concentrations in non-diabetic subjects. However these findings should be interpreted with caution because folate intake may simply reflect a healthy dietary pattern. CONCLUSIONS: These novel results suggest that the association of the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes depends on diet and that a high adherence to the MedDiet counteracts the genetic predisposition

Seafood Consumption, Omega-3 Fatty Acids Intake, and Life-Time Prevalence of Depression in the PREDIMED-Plus Trial

Background: The aim of this analysis was to ascertain the type of relationship between fish and seafood consumption, omega-3 polyunsaturated fatty acids (ω-3 PUFA) intake, and depression prevalence. Methods: Cross-sectional analyses of the PREDIMED-Plus trial. Fish and seafood consumption and ω-3 PUFA intake were assessed through a validated food-frequency questionnaire. Self-reported life-time medical diagnosis of depression or use of antidepressants was considered as outcome. Depressive symptoms were collected by the Beck Depression Inventory-II. Logistic regression models were used to estimate the association between seafood products and ω-3 PUFA consumption and depression. Multiple linear regression models were fitted to assess the association between fish and long-chain (LC) ω-3 PUFA intake and depressive symptoms. Results: Out of 6587 participants, there were 1367 cases of depression. Total seafood consumption was not associated with depression. The odds ratios (ORs) (95% confidence intervals (CIs)) for the 2nd, 3rd, and 4th quintiles of consumption of fatty fish were 0.77 (0.63–0.94), 0.71 (0.58–0.87), and 0.78 (0.64–0.96), respectively, and p for trend = 0.759. Moderate intake of total LC ω-3 PUFA (approximately 0.5–1 g/day) was significantly associated with a lower prevalence of depression. Conclusion: In our study, moderate fish and LC ω-3 PUFA intake, but not high intake, was associated with lower odds of depression suggesting a U-shaped relationship

Intracellular targeting of telomeric retrotransposon Gag proteins of distantly related Drosophila species

The retrotransposons that maintain telomeres in Drosophila melanogaster have unique features that are shared across all Drosophila species but are not found in other retrotransposons. Comparative analysis of these features provides insight into their importance for telomere maintenance in Drosophila. Gag proteins encoded by HeT-A[superscript mel] and TART[superscript mel] are efficiently and cooperatively targeted to telomeres in interphase nuclei, a behavior that may facilitate telomere-specific transposition. Drosophila virilis, separated from D. melanogaster by 60 MY, has telomeres maintained by HeT-A[superscript vir] and TART[superscript vir]. The Gag proteins from HeT-A[superscript mel] and HeT-A[superscript vir] have only 16% amino acid identity, yet several of their functional features are conserved. Using transient transfection of cultured cells from both species, we show that the telomere association of HeT-A[superscript vir] Gag is indistinguishable from that of HeT-A[superscript mel] Gag. Deletion derivatives show that organization of localization signals within the two proteins is strikingly similar. Gag proteins of TART[superscript mel] and TART[superscript vir] are only 13% identical. In contrast to HeT-A, surprisingly, TART[superscript vir] Gag does not localize to the nucleus, although TART[superscript vir] is a major component of D. virilis telomeres, and localization signals in the protein have much the same organization as in TART[superscript mel] Gag. Thus, the mechanism of telomere targeting of TART[superscript vir] differs, at least in a minor way, from that of TART[superscript mel]. Our findings suggest that, despite dramatic rates of protein evolution, protein and cellular determinants that correctly localize these Gag proteins have been conserved throughout the 60 MY separating these species.National Institutes of Health (U.S.) (Grant GM50315

The E3-ligases SCFPpa and APC/CCdh1 co-operate to regulate CENP-ACID expression across the cell cycle

Centromere identity is determined by the specific deposition of CENP-A, a histone H3 variant localizing exclusively at centromeres. Increased CENP-A expression, which is a frequent event in cancer, causes mislocalization, ectopic kinetochore assembly and genomic instability. Proteolysis regulates CENP-A expression and prevents its misincorporation across chromatin. How proteolysis restricts CENP-A localization to centromeres is not well understood. Here we report that, in Drosophila, CENP-ACID expression levels are regulated throughout the cell cycle by the combined action of SCFPpa and APC/CCdh1. We show that SCFPpa regulates CENP-ACID expression in G1 and, importantly, in S-phase preventing its promiscuous incorporation across chromatin during replication. In G1, CENP-ACID expression is also regulated by APC/CCdh1. We also show that Cal1, the specific chaperone that deposits CENP-ACID at centromeres, protects CENP-ACID from SCFPpa-mediated degradation but not from APC/CCdh1-mediated degradation. These results suggest that, whereas SCFPpa targets the fraction of CENP-ACID that is not in complex with Cal1, APC/CCdh1 mediates also degradation of the Cal1-CENP-ACID complex and, thus, likely contributes to the regulation of centromeric CENP-ACID deposition.MINECO [BFU2015-65082-P]; Generalitat de Catalunya [SGR2014-204, SGR2017-475]; European Community FEDER program; ‘Centre de Referència en Biotecnologia’ of the Generalitat de Catalunya. Funding for open access charge: MINECO [BFU2015-65082-P]; Generalitat de Catalunya [SGR2014-204, SGR2017-475]; European Community FEDER program

The zinc-finger proteins WOC and ROW play distinct functions within the HP1c transcription complex

In Drosophila, the Heterochromatin Protein 1c (HP1c) forms a transcriptional complex with the zinc-finger proteins WOC and ROW, and the extraproteasomal ubiquitin receptor Dsk2. This complex localizes at promoters of active genes and it is required for transcription. The functions played by the different components of the HP1c complex are not fully understood. In this study we show that WOC and ROW are required for chromatin binding of both Dsk2 and HP1c. However, while impairing chromatin binding strongly destabilizes HP1c, it does not affect Dsk2 stability. We also show that WOC, but not ROW, is required for nuclear localization of Dsk2. Moreover, WOC and Dsk2 co-immunoprecitate upon ROW depletion. These results suggest that WOC and Dsk2 interact to form a subcomplex that mediates nuclear translocation of Dsk2. We also show that ROW mediates chromatin binding of the WOC/Dsk2 subcomplex, as well as of HP1c. Altogether these observations favor a model by which the interaction with WOC recruits Dsk2 to the HP1c complex that, in its turn, binds chromatin in a ROW-dependent manner.This work was supported by grants from MICINN (BFU2015-65082-P and PGC2018-094538-B-100), the “Generalitat de Catalunya” (SGR2017-475) and the European Community FEDER program. This work was carried out within the framework of the “Centre de Referència en Biotecnologia” of the “Generalitat de Catalunya”. GDM acknowledges receipt of a “Severo Ochoa” FPI fellowship from MINECO