Fig. 5

Lamin A mutations causing laminopathies alter peripheral and internal nuclear architecture. a Nuclear envelope deformations in the nuclei of patients bearing the FLPD2-causing lamin A (R482W) mutation. Note the nuclear blebs essentially devoid of lamin B (arrows); reproduced from [20] with permission. b The lamin A (R482W) mutant elicits chromatin rearrangements at the nuclear periphery and in the nuclear interior in patient cells and in stem cell models of FPLD2 [14, 111, 112]. Whereas peripheral A-LADs are moderately affected at the nuclear periphery, punctual (non-LAD) lamin A interactions with promoters and enhancers in the nuclear interior are impaired in cells expressing lamin A (R482W). In wild-type cells (left), a weakly H3K27-acetylated developmentally regulated promoter bound by lamin A is inactivated during differentiation, in association with increased lamin A binding and H3K27 methylation. In mutant cells (right), defective binding of lamin A (R482W) coincides with expression of the gene in the undifferentiated state, and unscheduled overexpression and H3K27 acetylation after induction of differentiation. Differentiation is, however, abortive [111, 112]