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EMR-1/emerin is involved in tissue-specific anchoring of chromatin to the nuclear envelope and neuromuscular junction activity

AuthorsMuñoz-Jiménez, Celia; Ayuso, Cristina ; Askjaer, Peter
Issue Date2017
Citation21st International C. elegans Conference (2017)
AbstractThe nuclear envelope (NE) regulates transport of macromolecules between the nucleus and the cytoplasm and plays critical roles in nuclear organization and gene expression. Reflecting the importance of its functions, several human diseases are attributed to alterations in NE structure. Most notably are the laminopathies, with one example being Emery-Dreifuss muscular dystrophy (EDMD), which is caused by mutations in the inner nuclear membrane protein emerin or in the nuclear lamina protein lamin A. We have found recently that EMR-1, the Caenorhabditis elegans ortholog of emerin, associates with genes implicated in muscle and nervous system function and regulate their expression. Interestingly, deletion of emr-1 causes local changes in nuclear architecture and hypersensitivity to the cholinesterase inhibitor aldicarb, indicating altered activity at neuromuscular junctions. Although many NE proteins are ubiquitously expressed, laminopathies often affect a single tissue. It is hypothesized that tissue-specific alterations in nuclear organization might be responsible for particular symptoms of laminopathies. For this reason, we have developed novel tools to study changes in interactions between NE proteins and chromatin in a tissue-specific manner in intact animals. We report here the results of DamID experiments based on FLP-mediated recombination to dissect the function of EMR-1 in tissue-specific nuclear organization. Interestingly, EMR-1 interaction profiles in muscles vs. neurons reveal both many common domains and local changes in chromatin organization, with central part of chromosomes interacting more frequently with EMR-1 in neurons than in muscles. We are currently addressing the role of EMR-1 in regulation of gene expression in a tissue-specific way to understand the contribution of this protein to the neuromuscular junction activity and potentially to unravel the etiology of EDMD. It has been reported that NE morphology is prone to suffer from changes during normal aging and in progeria patients. Again, it has been proposed that alterations in nuclear organization through development and aging may have an impact on the aging-associated disorders. By performing FLP-mediated temporal DamID in young vs. old animals we have detected that chromatin accessibility changes dramatically in aged worms. Furthermore, we have identified local changes in EMR-1 interaction profiles in aged vs. young animals, with depletion of EMR-1 in central part of chromosomes in old animals.
DescriptionResumen del trabajo presentado a la 21st International C. elegans Conference of the Genetics Society of America, celebrada en California, Los Angeles (US) del 21 al 25 de junio de 2017.
Appears in Collections:(CABD) Comunicaciones congresos
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