Intermediate DNA methylation is a conserved signature of genome regulation

The role of intermediate methylation states in DNA is unclear. Here, to comprehensively identify regions of intermediate methylation and their quantitative relationship with gene activity, we apply integrative and comparative epigenomics to 25 human primary cell and tissue samples. We report 18,452 intermediate methylation regions located near 36 of genes and enriched at enhancers, exons and DNase I hypersensitivity sites. Intermediate methylation regions average 57 methylation, are predominantly allele-independent and are conserved across individuals and between mouse and human, suggesting a conserved function. These regions have an intermediate level of active chromatin marks and their associated genes have intermediate transcriptional activity. Exonic intermediate methylation correlates with exon inclusion at a level between that of fully methylated and unmethylated exons, highlighting gene context-dependent functions. We conclude that intermediate DNA methylation is a conserved signature of gene regulation and exon usage

Climate Change and American Bullfrog Invasion: What Could We Expect in South America?

BACKGROUND: Biological invasion and climate change pose challenges to biodiversity conservation in the 21(st) century. Invasive species modify ecosystem structure and functioning and climatic changes are likely to produce invasive species' range shifts pushing some populations into protected areas. The American Bullfrog (Lithobates catesbeianus) is one of the hundred worst invasive species in the world. Native from the southeast of USA, it has colonized more than 75% of South America where it has been reported as a highly effective predator, competitor and vector of amphibian diseases. METHODOLOGY/PRINCIPAL FINDINGS: We modeled the potential distribution of the bullfrog in its native range based on different climate models and green-house gases emission scenarios, and projected the results onto South America for the years of 2050 and 2080. We also overlaid projected models onto the South American network of protected areas. Our results indicate a slight decrease in potential suitable area for bullfrog invasion, although protected areas will become more climatically suitable. Therefore, invasion of these sites is forecasted. CONCLUSION/SIGNIFICANCE: We provide new evidence supporting the vulnerability of the Atlantic Forest Biodiversity Hotspot to bullfrog invasion and call attention to optimal future climatic conditions of the Andean-Patagonian forest, eastern Paraguay, and northwestern Bolivia, where invasive populations have not been found yet. We recommend several management and policy strategies to control bullfrog invasion and argue that these would be possible if based on appropriate articulation among government agencies, NGOs, research institutions and civil society

Polycomb-mediated silencing in neuroendocrine prostate cancer

BACKGROUND: Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype of prostate cancer (PCa) for which the median survival remains less than a year. Current treatments are only palliative in nature, and the lack of suitable pre-clinical models has hampered previous efforts to develop novel therapeutic strategies. Addressing this need, we have recently established the first in vivo model of complete neuroendocrine transdifferentiation using patient-derived xenografts. Few genetic differences were observed between parental PCa and relapsed NEPC, suggesting that NEPC likely results from alterations that are epigenetic in nature. Thus, we sought to identify targetable epigenetic regulators whose expression was elevated in NEPC using genome-wide profiling of patient-derived xenografts and clinical samples. RESULTS: Our data indicate that multiple members of the polycomb group (PcG) family of transcriptional repressors were selectively upregulated in NEPC. Notably, CBX2 and EZH2 were consistently the most highly overexpressed epigenetic regulators across multiple datasets from clinical and xenograft tumor tissues. Given the striking upregulation of PcG genes and other transcriptional repressors, we derived a 185-gene list termed 'neuroendocrine-associated repression signature' (NEARS) by overlapping transcripts downregulated across multiple in vivo NEPC models. In line with the striking upregulation of PcG family members, NEARS was preferentially enriched with PcG target genes, suggesting a driving role for PcG silencing in NEPC. Importantly, NEARS was significantly associated with high-grade tumors, metastatic progression, and poor outcome in multiple clinical datasets, consistent with extensive literature linking PcG genes and aggressive disease progression. CONCLUSIONS: We have explored the epigenetic landscape of NEPC and provided evidence of increased PcG-mediated silencing associated with aberrant transcriptional regulation of key differentiation genes. Our results position CBX2 and EZH2 as potential therapeutic targets in NEPC, providing opportunities to explore novel strategies aimed at reversing epigenetic alterations driving this lethal disease