An ambitious EC-funded research initiative on epigenetics advancing towards systems biology

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%)