RESEARCH ARTICLE Mapping of lamin A- and progerin-interacting genome regions

components of the nuclear lamina, cause a large group of phenotypically diverse diseases collectively referred to as lam-inopathies. These conditions often involve defects in chromatin organization. However, it is unclear whether A-type lamins interact with chromatin in vivo and whether aberrant chroma-tin–lamin interactions contribute to disease. Here, we have used an unbiased approach to comparatively map genome-wide interactions of gene promoters with lamin A and progerin, the mutated lamin A isoform responsible for the premature aging disorder Hutchinson–Gilford progeria syndrome (HGPS) in mouse cardiac myoytes and embryonic fibroblasts. We find that lamin A-associated genes are predominantly transcription-ally silent and that loss of lamin association leads to the relo-cation of peripherally localized genes, but not necessarily to their activation. We demonstrate that progerin induces global changes in chromatin organization by enhancing interactions with a specific subset of genes in addition to the identified lamin A-associated genes. These observations demonstrate disease-related changes in higher order genome organization in HGPS and provide novel insights into the role of lamin– chromatin interactions in chromatin organization. Abbreviations AIRE Autoimmune regulator ANOVA One-way analysis of variance BAC Bacterial artificial chromosome BPTF Bromeodomain and plant homeo-domain transcription facto