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This Week in PNAS: Mar 21, 2017

In the early, online version of the Proceedings of the National Academy of Sciences, a team from China, the US, and Canada tracks transcriptional patterns across the cell cycle in breast cancer cell lines. With the help of RNA sequencing, chromatin immunoprecipitation sequencing, and global nuclear run-on sequencing (GRO-seq), the researchers profiled the transcripts, histone modifications, and other regulatory features at play during the G0/G1, G1/S, and M phases of the cell cycle. "[O]ur analysis identified thousands of enhancer RNAs and related transcription factors that are highly correlated with cell cycle-regulated transcription," the authors note, "but not with steady-state expression, thus highlighting the importance of transcriptional and epigenetic dynamics during cell cycle progression."

Researchers from the Netherlands, the US, the UK, and Indonesia describe a role for the smooth muscle-expressed gene LMOD1 in a rare condition called megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS), which is marked by problems affecting visceral smooth muscle in the bladder, intestine, and other tissues. The team did array-based copy number profiling, homozygosity mapping, and exome sequencing to search for genetic culprits in an MMIHS case from the Netherlands, uncovering a premature stop codon-causing mutation in LMOD1. In follow-up experiments in mice, bladder, gastrointestinal, and other problems arose when the affected child's mutation was introduced by CRISPR-Cas9-based editing.

A University of California, San Diego-led team explores a form of methylation called non-CG methylation, which was previously associated with sex-specific neuronal epigenetic patterns. Using bisulfite sequencing, the researchers profiled non-CG and CG methylation in frontal cortex brain samples in female mouse models of X chromosome inactivation. Their results revealed non-CG methylation differences between active and inactive versions of the X chromosome: the active versions of the female sex chromosome were dappled with non-CG methylation marks, while non-CG methylation tended to be limited to regions escaping inactivation on muted X chromosomes.