MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures

Long noncoding RNAs (lncRNAs) regulate gene expression by association with chromatin, but how they target chromatin remains poorly understood. We have used chromatin RNA immunoprecipitation-coupled high-throughput sequencing to identify 276 lncRNAs enriched in repressive chromatin from breast cancer cells. Using one of the chromatin-interacting lncRNAs, MEG3, we explore the mechanisms by which lncRNAs target chromatin. Here we show that MEG3 and EZH2 share common target genes, including the TGF-β pathway genes. Genome-wide mapping of MEG3 binding sites reveals that MEG3 modulates the activity of TGF-β genes by binding to distal regulatory elements. MEG3 binding sites have GA-rich sequences, which guide MEG3 to the chromatin through RNA-DNA triplex formation. We have found that RNA-DNA triplex structures are widespread and are present over the MEG3 binding sites associated with the TGF-β pathway genes. Our findings suggest that RNA-DNA triplex formation could be a general characteristic of target gene recognition by the chromatin-interacting lncRNAs

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services

Monitoring of working and health condition in victims of bullying at work

Sono descritti gli effetti negativi sullo stato di salute e sulle caratteristiche di personalit\ue0 delle vittime di mobbing che si modificano positivamente nel caso di miglioramento della condizione lavorativa

A Long ncRNA Links Copy Number Variation to a Polycomb/Trithorax Epigenetic Switch in FSHD Muscular Dystrophy

Repetitive sequences account for more than 50% of the human genome. Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disease associated with reduction in the copy number of the D4Z4 repeat mapping to 4q35. By an unknown mechanism, D4Z4 deletion causes an epigenetic switch leading to de-repression of 4q35 genes. Here we show that the Polycomb group of epigenetic repressors targets D4Z4 in healthy subjects and that D4Z4 deletion is associated with reduced Polycomb silencing in FSHD patients. We identify DBE-T, a chromatin-associated noncoding RNA produced selectively in FSHD patients that coordinates de-repression of 4q35 genes. DBE-T recruits the Trithorax group protein Ash1L to the FSHD locus, driving histone H3 lysine 36 dimethylation, chromatin remodeling, and 4q35 gene transcription. This study provides insights into the biological function of repetitive sequences in regulating gene expression and shows how mutations of such elements can influence the progression of a human genetic disease

Drosophila suzukii daily dispersal between distinctly different habitats

Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) is an insect pest originating in South-East Asia that has invaded Europe (EU) and the Americas. This insect has caused extensive economic damage to the soft fruit industry in all countries to which it has spread. Drosophila suzukii population management relies primarily on chemical pesticides, an approach with serious drawbacks including the risk of residues on fruit and development of insecticide resistance. Drosophila suzukii dispersal from surrounding vegetation is believed to significantly increase the risk of crop damage. Despite increasing evidence that environmental configuration and composition strongly affect D. suzukii population levels and activity, the effects of landscape and abiotic factors including temperature and humidity on its movement is still poorly understood. For this reason, during the summer of 2017, we employed a mark-capture strategy using protein markers during middle July and early August. Within the experimental setup, flies were captured in food-baited traps, and later analyzed for the presence of the marker through an ELISA procedure. Our data suggest that more suitable temperature, humidity, and a diverse suite of alternative hosts found in the surrounding forest vegetation likely drove the recorded dispersion. Most of the captured D. suzukii marked within the crop were collected in surrounding forest vegetation within 24 hours of the marking event during each of the periods of collection. Results strongly indicated how humidity, temperature and alternative hosts are key drivers of D. suzukii populations in different habitat

Active chromatin marks drive spatial sequestration of heterochromatin in C. elegans nuclei

The execution of developmental programs of gene expression requires an accurate partitioning of the genome into subnuclear compartments, with active euchromatin enriched centrally and silent heterochromatin at the nuclear periphery1. The existence of degenerative diseases linked to lamin A mutations suggests that perinuclear binding of chromatin contributes to cell-type integrity2,3. The methylation of lysine 9 of histone H3 (H3K9me) characterizes heterochromatin and mediates both transcriptional repression and chromatin anchoring at the inner nuclear membrane4. In Caenorhabditis elegans embryos, chromodomain protein CEC-4 bound to the inner nuclear membrane tethers heterochromatin through H3K9me3,5, whereas in differentiated tissues, a second heterochromatin-sequestering pathway is induced. Here we use an RNA interference screen in the cec-4 background and identify MRG-1 as a broadly expressed factor that is necessary for this second chromatin anchor in intestinal cells. However, MRG-1 is exclusively bound to euchromatin, suggesting that it acts indirectly. Heterochromatin detachment in double mrg-1; cec-4 mutants is rescued by depleting the histone acetyltransferase CBP-1/p300 or the transcription factor ATF-8, a member of the bZIP family (which is known to recruit CBP/p300). Overexpression of CBP-1 in cec-4 mutants is sufficient to delocalize heterochromatin in an ATF-8-dependent manner. CBP-1 and H3K27ac levels increase in heterochromatin upon mrg-1 knockdown, coincident with delocalization. This suggests that the spatial organization of chromatin in C. elegans is regulated both by the direct perinuclear attachment of silent chromatin, and by an active retention of CBP-1/p300 in euchromatin. The two pathways contribute differentially in embryos and larval tissues, with CBP-1 sequestration by MRG-1 having a major role in differentiated cells.We thank the Caenorhabditis Genetics Center (CGC) of the NIH Office of Research Infrastructure Programs (P40 OD010440) for strains, S. Strome for the immunofluorescence protocol and H. Kimura for the H3K36me2 antibody. We are grateful to I. Katiç and R. Sack for invaluable technical support. We thank C. Schmid and FMI facilities as well as EMBL GeneCore for advice and support. D.S.C. was supported by an EMBO Long Term Fellowship and a FP7 Marie Curie Action Intra-European Fellowship. J.P. was supported by an EMBO Long Term Fellowship. C.M.-J. and P.A. thank the Spanish Ministry of Economy and Competitiveness for support (BFU2016-79313-P and MDM-2016-0687). S.M.G. thanks the Swiss National Science Foundation and the Novartis Research Foundation for support. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation programme (Epiherigans - grant agreement No 743312)