Mammalian PRC2 contains one of three Polycomb-like proteins, PHF1, PHF19 or MTF2. Three papers in this issue provide insight into the mechanisms by which PHF19 and PHF1 contribute to PRC2-mediated gene repression, showing that specific binding of the Tudor domains of PHF19 and PHF1 to H3K36me3 recruits PRC2 to active genes. Cover image contributed by the Di Croce laboratory and designed by Iris Joval Granollers. pp 1257–1265, 1266–1272 and 1273–1281; News and Views p 1214

Promoter-proximal pausing by RNA polymerase II ensures genespecific regulation and RNA quality control. Fisher and colleagues show that Cdk7 activity controls pause establishment by stimulating the TFIIE to DSIF switch at the promoter, and pause release and elongation through activation of Cdk9 (P-TEFb). Cover art by Patrick Larochelle, based on an original photograph by Stephen Alexander (www.temporarytemples.co.uk). pp 1108–1115

Jenuwein and colleagues propose a transcription factor (TF)-based model for heterochromatin formation. On the cover, this model is illustrated by the Matterhorn of the Swiss Alps, which resembles the sharp TF peaks found at promoters. Les Droites of the Mont Blanc are reminiscent of reiterated TF binding sites within heterochromatin. Cover images provided by the Jenuwein laboratory. pp 1023–1030, News and Views p 973

Kinetochores are large structures that assemble onto centromeric DNA. The architecture of the yeast kinetochore particle is now studied by electron microscopy and electron tomography, revealing a large central hub surrounded by five spokes containing multiple attachment sites for microtubules. The cover image is an artistic representation of the kinetochore. Artwork by Nathan A. Gonen. pp 925–929

The cover image of an Escherichia coli colony stochastically expressing single fluorescent protein molecules that are visualized as individual spots on the cell membrane highlights the heterogeneity of gene expression in different cells and emphasizes the necessity for cells to control noise in gene expression, a topic examined in detail by Wang, Xiao and colleagues. Image created by Zach Hensel. pp 797–802

Mammalian dioxygenase ALKBH2 searches the genome for alkylation lesions and mediates their direct repair. He and colleagues now show that ALKBH2 probes the stability of base pairs to find DNA damage, and its oxidative demethylation mechanism ensures that only cognate lesions are processed, similar to the mechanism of gear wheels for a safe lock. Image by John A. Shaw from Shutterstock. pp 671–676

Understanding the mechanisms that control mRNA decoding by ribosomes during the process of translation remains a major challenge. This Focus issue contains a series of Reviews and a Perspective on the theme of Translational Control. On the cover, detail of an Enigma machine is shown. Cover image by Christopher Stokes from iStockphoto. pp 559–602

Bryant and colleagues find that DNA gyrase uses a branched kinetic pathway for coupling energy consumption to mechanical work, similar to the diverging and converging stream shown here. Cover art by Martin McCarthy from iStockphoto. pp 538–546

Karlseder and colleagues show that prolonged mitotic arrest leads to telomere deprotection, triggering the DNA damage response and resulting in cell-cycle arrest or cell death. Taxol, the mitosis inhibitor used in some cancer treatments, is isolated from the bark of the Pacific Yew (Taxus brevifolia) shown here. Cover art by Erin Dewalt. pp 387–394

Soutoglou and colleagues investigate how DNA double strand breaks (DSBs) affect transcription elongation. The introduction of a single DSB within transcribed genes stalls RNAPII and inhibits transcription elongation and reinitiation, in a manner dependent on DNAPK and the proteasome. Image by David Chadwick from iStockphoto. pp 276–282

Asymmetric dimethylation of histone H3 arginine 2 is known to repress transcription. Guccione and colleagues now report that symmetric dimethylation of the same residue recruits the coactivator complex component WDR5, keeping genes poised for transcription. Image by tunart from www.istockphoto.com. pp 136–144

Variants of the extracellular chaperone clusterin have been linked to susceptibility to Alzheimer's disease. Wilson, Dobson, Klenerman and colleagues now show that clusterin sequesters Ab1–40 oligomers and prevents their further aggregation. Photograph from www.istockphoto.com. pp 79–83.