Gradual Unpacking: Eukaryotic DNA is packaged onto nucleosomes, which form the main constituent of chromatin. This packaging material presents a barrier to accessing the genome by the various machineries that need to deal with the DNA: replication, recombination, repair, and transcription complexes, for example. Hodges et al. (p. 626 ; see the Perspective by Otterstrom and van Oijen ) use single-molecule techniques to analyze how a yeast RNA polymerase II ternary elongation complex copes when it encounters a single nucleosome directly in its path. The polymerase does not actively peel the DNA from the nucleosome's surface but, instead, waits patiently until the DNA fluctuates off the nucleosome and then advances, increment by increment, until the nucleosome is destabilized. Under certain conditions the destabilized nucleosome, rather than being lost entirely from the DNA, can be passed back to the DNA behind the polymerase.

During the last decade, a host of epigenetic mechanisms were found to contribute to cancer and other human diseases. Several genomic studies have revealed that ∼20% of malignancies have alterations of the subunits of polymorphic BRG-/BRM-associated factor (BAF) and Polybromo-associated BAF (PBAF) complexes, making them among the most frequently mutated complexes in cancer. Recurrent mutations arise in genes encoding several BAF/PBAF subunits, including ARID1A, ARID2, PBRM1, SMARCA4, and SMARCB1. These subunits share some degree of conservation with subunits from related adenosine triphosphate (ATP)-dependent chromatin remodeling complexes in model organisms, in which a large body of work provides insight into their roles in cancer. Here, we review the roles of BAF- and PBAF-like complexes in these organisms, and relate these findings to recent discoveries in cancer epigenomics. We review several roles of BAF and PBAF complexes in cancer, including transcriptional regulation, DNA repair, and regulation of chromatin architecture and topology. More recent results highlight the need for new techniques to study these complexes.