Spreading of silent chromatin: inaction at a distance

One of the oldest unsolved problems in genetics is the observation that gene silencing can 'spread' along a chromosome. Although spreading has been widely perceived as a process of long-range assembly of heterochromatin proteins, such 'oozing' might not apply in most cases. Rather, long-range silencing seems to be a dynamic process, involving local diffusion of histone-modifying enzymes from source binding sites to low-affinity sites nearby. Discontinuous silencing might reflect looping interactions, whereas the spreading of continuous silencing might be driven by the processive movement of RNA or DNA polymerases. We review the evidence for the spreading of silencing in many contexts and organisms and conclude that multiple mechanisms have evolved that silence genes at a distance.