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Genome Research Papers on Microsatellite Indels in Cancer, Gene Regulation Analyses

A team from Japan shares findings from an effort to catalog microsatellite-impacting small insertions and deletions (indels) in nearly two dozen cancer types. Using whole-genome sequences for more than 2,700 tumor samples profiled for the International Cancer Genome Consortium and an indel caller known as MIMcall, the researchers uncovered tumor types and microsatellite sites that were recurrently altered by indels, along with potential markers for tumors with broader microsatellite instability (MSI). "Our analysis provides a comprehensive picture of mutations in the microsatellite regions," they report, "and reveals possible causes of mutations, as well as provides a useful marker set for MSI detection."

Researchers in the Netherlands and US explores interactions between transcription dynamics and shifts in binding at chromatin regulatory sites using a budding yeast model system and a previously reported barcode sequencing method called Epi-Decoder. "Epi-Decoder is a strategy for decoding the local proteome of a single genomic locus," the team says, noting that the approach "provides a powerful strategy for capturing the temporal binding dynamics of multiple chromatin proteins under varying conditions and cell states." In their own yeast experiments, for example, the authors found that dialing down transcription with RNA polymerase enzyme inhibitors appeared to correspond to a "broad rewiring of local chromatin proteomes," including a rise in chromatin remodeler binding and a dip in binding by core transcriptional proteins.

Finally, a team from the US and China presents an analytical approach for finding regulatory elements and untangling regulatory networks based on gene expression and corresponding chromatin accessibility profiles tracked over time. This "Time Course Regulatory Analysis," or TimeReg, software is intended to "prioritize regulatory elements, to extract core regulatory modules at each time point, to identify key regulators driving changes of the cellular state, and to causally connect the modules across different time points," the researchers note. When they applied TimeReg to paired RNA sequencing-based gene expression and ATAC-seq chromatin accessibility profiles from mouse embryonic stem cells during the process of progenitor cell differentiation, for example, the authors saw more than 57,000 new regulatory elements that appear to contribute to brain-related differentiation.