Chromatin architecture in lipodystrophic laminopathies

Info:Mutations in the lamin A (LMNA) gene, encoding lamin A/C, cause laminopathies, including familial partial lipodystrophies of type 2 (FPLD2). Partial lipodystrophies affects adipose tissue in a depot-specific manner and leads to insulin resistance, type-2 diabetes and other metabolic complications. Using patient-derived cells and engineered adipose stem cells expressing LMNA mutants, we investigate how FPLD2-causing LMNA mutations deregulate adipose progenitor cell nuclear envelope integrity, chromatin architecture and function. We combine cell biology, proteomics and high-throughput genomics approaches.

Project participants

Nolwenn Briand, Louise Petersen, Julia Madsen-Østerbye, Anita Sørensen; collaborations with Coen Campsteijn (U Oslo), Corinne Vigouroux and Isabelle Jéru (INSERM & Université Pierre et Marie Curie, Paris)

Ongoing research

Impact of FPLD2-causing lamin A p.R482W mutation on functional nuclear and chromatin architecture during adipogenesis and in adipocytes
Impact of lamin A p.R482W on nuclear envelope integrity

Recent achievements

FLPD2-causing lamin A p.R482W mutation deregulates vascular differentiation gene networks in an iPS cell model of FPLD2 (Briand, Guénantin 2018 Hum Moll Genet)
Lamin A p.R482W alters radial positioning of loci in FPLD2 patient fibroblasts (Paulsen 2017 Genome Biol)
Lamin A mutation deregulates epigenetic and spatial conformation of anti-adipogenic MIR335 locus (Oldenburg 2017 J Cell Biol)
ChIP protocol for nuclear lamins (Oldenburg 2016 Meth Mol Biol)
Lamin A mutation deregulates SREBP1 activity in FPLD2 (Vadrot 2015 Hum Mol Genet)
Lamin A mutation alters lamin A interactome of and deregulates FXR1 (Oldenburg 2014 Hum Mol Genet)