Stochastic epigenetic control of obesity


Project Summary

Current estimates place the prevalence of obesity beyond 1.2 billion people by the year 2030. We have recently begun generating conditional mouse mutants for chromatin regulating obesity candidate genes. One of these, a “Momme” gene, was recently identified as capable of modulating epigenetically silenced states in vivo in mice. Intriguingly, at random temporal intervals ~30% of the haploinsufficient mice exhibit rapid, overt obesity in adulthood. Through tissue- and time-specific knockouts and an array of molecular approaches we aim to identify the tissue source(s) and molecular underpinnings of this first example of stochastic mammalian metabolic disease.

Project-relevant publications

  • Ost A., Lempradl A., Casas E., Weigert M., Tiko T., Deniz M., Pantano L., Boenisch U., Itskov P.M., Stoeckius M., Ruf M., Rajewsky N., Reuter G., Iovino N., Ribeiro C., Alenius M., Heyne S., Vavouri T. and Pospisilik J.A. (2014) Paternal diet defines offspring chromatin state and intergenerational obesity. Cell 159, 1352-1364.
  • Teperino R., Lempradl A. and Pospisilik J.A. (2013) Bridging epigenomics and complex disease: the basics. Cell Mol Life Sci 70, 1609-1621.
  • Pospisilik J.A. (2013) Metabolism shaping chromatin shaping metabolism. Cell Mol Life Sci 70, 1493-1494.