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. 2010 Dec 13;191(6):1049–1060. doi: 10.1083/jcb.201007028

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© 2010 Cabianca and Gabellini

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Figure 4. — Epigenetic features at 4q35 in healthy subjects and FSHD patients. In control individuals, the D4Z4 repeat array is characterized by markers of chromatin repression, such as high levels of DNA methylation, SUV39H1-mediated H3K9me3, and EZH2-mediated H3K27me3. In contrast, FSHD patients display hypomethylation, loss of H3K9me3, and corresponding loss of HP1γ and cohesin binding. In healthy subjects, D4Z4 is specifically bound by EZH2 and a repressor complex composed of YY1, HMGB2, and nucleolin. It is still to be determined whether binding of these factors is altered in FSHD patients. The human 4q is perinuclear in both control and FSHD individuals. This localization depends on a region that is proximal to D4Z4 in healthy subjects but is D4Z4-specific and CTCF-mediated in FSHD patients. A MAR located upstream of the repeat array was found to be weakened in FSHD, altering the 3D chromosomal architecture of the region.