Model for the nucleosome remodeling function of Isw1. (a) Isw1 is recruited (or activated) by particular histone modifications (red stars; possibly H3K79me3) at mid-coding regions and repelled (or inhibited) by other modifications around the TSS (green stars). Isw1 generates a nucleosomal barrier (illustrated as thick nucleosome edges) that transiently delays PolII and facilitates its interaction with mRNA processing factors. This activity of Isw1 (and/or the presence of a delayed PolII) slides the Isw1-regulated nucleosome downstream towards an energetically less favorable position, which is opposite to the normal effect of PolII on nucleosomes. Isw2 performs a similar function but at the transcription termination (or start) nucleosomes, due to interactions with different factors and histone modifications (purple stars), suggesting a division of labor between Isw1 and Isw2. (b) In Δisw1 cells, chromatin structure within the coding region is less repressive, thus impairing PolII interaction with processing factors and allowing cryptic initiation. No linker is found between the Isw1-dependent nucleosome at the mid-coding region and its adjacent upstream nucleosome, perhaps indicating that these nucleosomes invade DNA territories occupied by their neighbors  or that they are held together by an unknown mechanism. WT, wild type.