Fig. 6

Epigenetic deregulation of lamina-associated domains (LADs) in HGPS. Progerin-driven nuclear malformation in HGPS nuclei causes substantial, but potentially locally stochastic epigenetic reconfiguration of LAD-specific chromatin. As peripheral heterochromatin is diminished in these cells, many of the affected regions gain a more relaxed chromatin environment that is more permissive to the binding of transcription factors and might thus facilitate differential expression. In some cases, chromatin decondensation and disease-specific differential expression of formerly LAD-associated loci coincides with their relocalization within the nucleus, as detected in the case of EDIL3 and IGFBP7