Silenced and escape regions have distinct chromatin marks. (a) Chromatin containing escape genes is excluded from the condensed heterochromatic body of the Xi. In mouse, individual escape genes are surrounded by inactivated chromatin. In contrast, human escape genes exist in domains comprising clusters of genes. Orange bars represent escape genes and blue bars inactivated genes. (b) Silenced chromatin in the Xi is coated by Xist RNA potentially via specific DNA motifs (green). Repressive histone modifications and histone variants (for example, H3K27me3, H3K9me3, H4K20me3, and macroH2A1) are recruited and DNA methylation modifies the CpG islands. This type of chromatin structure prevents transcription (blue bar below). In contrast, escape gene regions are enriched for permissive histone marks (for example, H3K4me3, and H3 and H4 acetylation) and RNA polymerase II (RNA pol II) and are hypomethylated at their CpG islands. Insulator sites bound by the insulator protein CTCF, together with unknown factors (as denoted by the '?'), may separate inactivated genes (blue bar) from active genes (orange bar). CTCF binding may block CpG methylation and the spread of repressive chromatin and/or may organize the chromatin into loops.