Nuclear architecture in lipodystrophic laminopathies

Project participants

Nolwenn Briand, Louise Petersen, Evdokiia Potolitsyna, Kristin Vekterud; collaboration with Corinne Vigouroux (INSERM & Université Pierre et Marie Curie, Paris)

Image: Dual-color fluorescence in situ hybridization visualization of the miRNA MIR335 gene (red) and an enhancer 200 kb upstream (green) in adipose progenitors expressing wild-type lamin A or an FPLD2 lamin A mutant. Enhancer-gene proximity in  these cells correlates with MIR335 expression. MIR335 is an anti-adipogenic miRNA (among other things).

Ongoing research

  • Mechanistic impact of the FPLD2-causing lamin A p.R482W mutation on nuclear architecture and gene regulation in adipose progenitors
  • Deregulation of spatial chromatin organization by the lamin A p.R482W mutation in adipose progenitors and adipocytes
  • Impact of the lamin A p.R482W mutation on nuclear envelope integrity in differentiating adipocytes

Recent achievements

  • Lipodystrophic lamin A p.R482W mutation deregulates vascular differentiation gene networks in an iPS cell model of FPLD2 (Briand, Guénantin 2018 Hum Mol Genet 27, 1447-1459)
  • Lipodystrophic lamin A mutation alters radial positioning of loci in FPLD2 patient fibroblasts (Paulsen 2017 Genome Biol 18, 21)
  • Lipodystrophic lamin A p.R482W mutation deregulates epigenetic and spatial conformation of anti-adipogenic MIR335 locus and adipocyte differentiation Oldenburg 2017 J Cell Biol  216, 2731-2743)
  • ChIP protocol for nuclear lamins (Oldenburg 2016 Meth Mol Biol 1411, 315-324)
  • The lamin A p.R482W mutation alters the lamin A interactome of and deregulates FXR1 (Oldenburg 2014 Hum Mol Genet 23, 1151-1162)