Fig. 6. General (left) and specific views (right) of how transcriptional activity is regulated by local (A,B) and distant motifs (C-F). Left: thick and thin blue lines represent transcription units (with promoters as white circles) and intervening DNA, respectively. Right: half a loop is shown with unit t temporarily attached to, and transcribed by, a polymerase in a factory (pink circle); as a transcript is extruded (wavy red line), chromatin between s and t is reeled in and `opened'. (A,B) Left: a repressor (or activator) binds close to the transcription start site to reduce (increase) the chances that a polymerase will be recruited. Right: repressor (or activator) binding to the promoter of s reduces (increases) the chances that s binds to the factory. In both cases, the repressor (or activator) has the same effect by binding to the polymerase (rather than the promoter). (C) Left: inserting a nontranscribed motif (e.g. some enhancers) increases the activity of a distant unit. Right: the motif has an affinity for transcription factors in the factory, and – once it binds – promoter s becomes tethered close to the factory, increasing its chances of attaching and initiating. A nontranscribed silencer (not shown) could have the opposite effect and reduce the chances that promoter s could bind (perhaps by directly blocking access to polymerases in the factory, or indirectly because DNA between the motif and promoter s was too short/rigid to loop back). (D) Left: inserting a transcribed motif (e.g. some enhancers, LCRs) increases the activity of a distant unit. Right: unit s attaches to the factory and initiates; this brings promoter r closer to the factory, increasing its chances of attaching and initiating. If the orientation of s were reversed, its transcription would progressively tether r ever closer to the factory and this might explain why orientation affects the activity of the ß-globin LCR (Tanimoto et al., 1999). (E) Left: inserting an active unit near another, silences one of the two. Right: the attachment of unit t prevents s from attaching, perhaps because all polymerases are now occupied, DNA between t and s is too short/rigid to loop back, or transcription of t leads to recruitment of inappropriate factors to the factory; alternatively, r might attach to another (blue) factory lacking the polymerase and/or factors required by s, so distancing s from the (pink) factory with the appropriate polymerase/factors (tRNA^Thr in HMR probably silences URA3 like this). (F) Left: Heterochromatin spreads leftwards (grey arrow) down the fibre, but inserting a barrier (yellow) restricts the spread and allows the unit to be expressed. Right: unit t acts as a barrier preventing heterochromatic spread to inactivate s.