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Genome Research Papers on Cancer Chromatin, Splicing in the Thymus, Circular RNAs in Cancer

A team from the US, France, and Australia investigates chromatin sites carrying histone modification marks linked to both transcriptional activation and repression — "bivalent chromatin" sites with potential roles in development and cancer. "Most gene promoters DNA-hypermethylated in adult human cancer are bivalently marked in [embryonic stem cells]," the researchers write. Based on available epigenetic data and their own experiments in pluripotent human and mouse embryonic stem cells, they suggest that promoters with both the H3K4me3 transcriptional activation and the repressed chromatin-related H3K27me3 marks may be protected against de novo DNA methylation. "Altogether," they write, "our findings suggest that bivalency protects reversibly repressed genes from irreversible silencing and that loss of H3K4me3 may make them more susceptible to aberrant DNA methylation in diseases such as cancer."

Researchers at the University of Oxford, the University of Basel, and ETH Zurich describe a role for RBFOX splicing factors in messenger RNA splicing in thymic epithelial cells (TEC), which in turn influence the collection of antigens targeted by immune T cells. With the help of deep, stranded RNA sequencing, the team tracked mRNA splicing patterns in immature and mature mouse medullary TECs, comparing them to splicing profiles in 21 other tissues in mice to identify RBFOX and other mTEC splicing factors to explore further. "Using a conditional loss-of-function approach, we show that RBFOX2 promotes mTEC development and regulates the alternative splicing of promiscuously expressed genes," the authors report. "These data indicate that TEC recommission a small number of peripheral [splicing factors], including members of the RBFOX family, to generate a broad but selective representation of the peripheral splice isoform repertoire."

Finally, a team from the Chinese University of Hong Kong and the University of Malaysia outlines a strategy dubbed psirc for analyzing RNA sequence data to unearth and tally the expression of full-length circular RNAs (circRNAs). After validating the approach with simulated and authentic data, the researchers used psirc to compare RNA-seq data from nasopharyngeal carcinoma and normal nasopharynx samples, identifying differentially expressed circRNA isoforms that appeared to distinguish the cancerous and non-cancerous samples.