Advancing Epigenetics Towards Systems Biology

Susan Gasser

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland

Functional organization of the nucleus

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susan gassersusan gasser group

The long-range organization of the genome contribute to both its programmed expression and its maintenance. We study how spatial organization of the interphase genome impinges on mechanisms of repair and replication fork stability, as well as epigenetic inheritance. We combine mapping of genome-wide factor binding sites, synthetic lethal screens, quantitative live fluorescence imaging, biochemical reconstitution and molecular genetics to examine how nuclear organization affects programmed gene expression in C. elegans. The exploitation of this model organism allows us to examine epigenetic inheritance through tissue differentiation in the intact organism.
We have confirmed a tissue-specific role for lamin in the maintenance of the muscle transcriptome, and a role for histone H3 K9 methylation in the positioning of heterochromatin domains. We are following up on the latter by screening for factors that mediate the association between H3K9 methylation and the nuclear lamina. EMS mutagenesis and RNAi depletion screens are underway. We monitor endogenous genes that are affected by loss of heterochromatin sequestration using the genome-wide methods, CHIP-seq and LMN-1 DAM-ID. Finally we will examine how the Y59C EDMD mutation in lamin causes myopathy by identifying muscle specific changes in gene expression and linking the changes in transcription to altered muscle phenotype.

Lab members involved:

  • Dr Vincent Dion - postdoc
  • Dr Helder Ferreira - postdoc
  • Dr Chihiro Horigome - postdoc
  • Dr Anna Mattout - postdoc
  • Benjamin Towbin - PhD student
  • Sabine Rohner - PhD student
  • Adriana Gonzalez - PhD student
  • Véronique Kalck - technician (80%)

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Latest publications

Spatial segregation of heterochromatin: uncovering functionality in a multicellular organism.

27187571 - 2016-05-18
Nucleus 2016 May 17;:0

Cabianca DS, Gasser SM

Nuclear Architecture: Past and Future Tense.

27177990 - 2016-05-15
Trends Cell Biol 2016 May 10;

Gasser SM

PolySUMOylation by Siz2 and Mms21 triggers relocation of DNA breaks to nuclear pores through the Slx5/Slx8 STUbL.

27056668 - 2016-04-09
Genes Dev 2016 Apr 15;30(8):931-45

Horigome C, Bustard DE, Marcomini I, Delgoshaie N, Tsai-Pflugfelder M, Cobb JA, Gasser SM

View all their publications