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This Week in Genome Research: Feb 28, 2018

In Genome Research this week, a University of Southern California team uses chromatin immunoprecipitation sequencing, RNA sequencing, and other approaches to characterize binding sites and related expression patterns of ZFX — a transcription factor previously implicated in tumor growth, proliferation, and cancer outcomes — in cell lines generated from kidney, colon, prostate, and/or breast cancers. From the thousands of ZFX binding sites identified in these cells, the researchers got a closer look at the types of promoters and regions where the transcription factor binds. For example, ZFX typically turned up at the promoters of genes with particularly high expression, while the expression of such genes tended to decline when they used small interfering RNA to curb ZFX activity in prostate and breast cancer cells.

Also this week, researchers from the University of Colorado at Boulder characterize short, unstable RNA transcripts called enhancer RNAs (eRNAs) that appear to mark enhancer regions with active transcription factors. The team turned to a so-called transcription fit, or Tfit, approach to get a look at bi-directional transcript initiation based on RNA polymerase II features and the enzyme's inferred loading sites. Based on the transcription factor binding activity, binding motifs, and eRNA initiation sites gleaned from Tfit analyses of GRO-seq and other data for many human and mouse cell lines, the authors argue that eRNAs "are a powerful readout" of transcription factor activity.

And finally, a team from the Whitehead Institute and the Massachusetts Institute of Technology take a look at sex chromosome evolution from autosomal chromosomes using insights gleaned from microRNA regulatory networks. Using miRNA target site phylogeny, the researchers retraced gene dosage sensitivity across ancestral autosomes that evolved to become mammalian X and Y chromosomes, looking at the characteristics of the genes that landed up being X-linked or Y-linked. "Pre-existing heterogeneities in dosage sensitivity, manifesting as differences in the extent of miRNA-mediated repression, predicted either the retention of a Y homolog or the acquisition of [X chromosome inactivation] following Y gene decay," they report, suggesting sex chromosome evolution is shaped in part by post-transcriptional regulation.