Mapping of lamin A- and progerin-interacting genome regions.

Nard Kubben, Michiel Adriaens, Wouter Meuleman, Jan W Voncken, Bas van Steensel, Tom Misteli

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Abstract

Mutations in the A-type lamins A and C, two major components of the nuclear lamina, cause a large group of phenotypically diverse diseases collectively referred to as laminopathies. These conditions often involve defects in chromatin organization. However, it is unclear whether A-type lamins interact with chromatin in vivo and whether aberrant chromatin-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 transcriptionally silent and that loss of lamin association leads to the relocation 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.
Original languageEnglish
Pages (from-to)447-464
Number of pages18
JournalChromosoma
Volume121
Issue number5
DOIs
Publication statusPublished - 2012

Cite this

Kubben, N., Adriaens, M., Meuleman, W., Voncken, J. W., van Steensel, B., & Misteli, T. (2012). Mapping of lamin A- and progerin-interacting genome regions. Chromosoma, 121(5), 447-464. https://doi.org/10.1007/s00412-012-0376-7