Figure 1. Chromatin involvement in repeat instability. Some chromatin-related mechanisms that lead to repeat instability are depicted. Bidirectional transcription of long CAG repeats generates double stranded RNA, which is processed by the RNAi machinery into short RNAs that form hairpins. Those short CAG RNAs promote heterochromatin production, resulting in transcription inhibition (Refs. 3 and 4). Double stranded RNA of CAG repeats can also induce apoptosis, leading to polyQ-related pathology (Refs. 7 and 8). Perturbed CTCF binding and low Dnmt1 expression levels were also reported to promote instability (Refs. 9 and 10).