Genome-wide analysis links emerin/EMR-1 to neuromuscular junction activity in C. elegans

Resumen del póster presentado en el European Worm Meeting: Berlin C. elegans Meeting, celebrado en Berlín del 3 al 5 de mayo de 2014.Laminopathies are caused by alterations in components of the nuclear envelope (NE). A well-known example is Emery-Dreifuss Muscular Dystrophy induced by mutations in the human lamin A/C and emerin genes. While most NE proteins are widely expressed throughout the organism, laminopathies affect only a subset of tissues. However, the molecular mechanisms that explain this phenomenon are still elusive, but are likely to include specific NE-chromatin interactions. We have performed genome wide DamID analysis in adult C. elegans nematodes comparing the DNA association profile of three NE components, lamin/LMN-1, emerin/EMR-1, and elys/MEL-28. LMN-1 constitutes the nuclear lamina, whereas EMR-1 is an integral nuclear membrane protein. MEL-28 is an essential component of nuclear pores but is also found in the nuclear interior. Although LMN-1 and EMR-1 both bound to transcriptionally inactive regions of the genome, EMR-1 showed a predominant role in the anchoring of muscle and neuronal genes to the nuclear periphery. In contrast, MEL-28 associated mainly with active genes. Deletion of either EMR-1 or LEM-2, another integral NE protein, caused local changes in nuclear architecture with both increased and decreased LMN-1-DNA association. Transcriptome analyses revealed that EMR-1 and LEM-2 promote gene repression, in particular of muscle and nervous system-related genes. Finally, performing aldicarb sensitivity experiments, we demonstrated that synapse activity at the neuromuscular junction was altered in emr-1 mutants. These data suggest a novel role of EMR-1 in neuromuscular tissues through the control of chromatin organization and gene expression and may contribute to elucidate Emery-Dreifuss Muscular Dystrophy etiology.Peer Reviewe