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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 CSIC ORCID; Dobrzynska, Agnieszka CSIC ORCID CVN; Askjaer, Peter CSIC ORCID
Issue Date13-Jun-2018
CitationEMBO workshop "C. elegans Development, Cell Biology & Gene Expression Meeting" (2018)
AbstractThe nuclear envelope (NE) regulates transport of macromolecules between the nucleus and the cytoplasm and plays critical roles in nuclear organization and gene expression. Specific chromatin domains are anchored to the NE, which generally is associated with formation of heterochromatin and transcriptionally silencing. Reflecting the importance of NE functions, a broad range of 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 recently found that EMR-1, the Caenorhabditis elegans ortholog of emerin, associates with genes implicated in muscle and nervous system function and regulates 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 (NMJ). 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. We suggested that emerin might regulate nuclear organization in a tissuespecific manner. For this reason, we developed a novel FLP-Frt-based DamID technique to study changes in interactions between EMR-1 and chromatin in specific cell types using intact animals as starting material. Interestingly, EMR-1 interaction profiles in muscles vs. neurons reveal both many common domains but also local changes in chromatin organization. Generally, most gene classes are more frequently in contact with EMR-1 in neurons as compared to muscles. Within the two tissues, silent genes are more associated with EMR-1 than active genes, although we also observed exceptions where EMR-1 was enriched at active genes. This suggests that EMR-1 might have both repressive and activating roles at the NE and we are testing how this influence NMJ activity.
DescriptionTrabajo presentado en EMBO workshop "C. elegans Development, Cell Biology & Gene Expression Meeting", celebrado en Barcelona (España) del 13 al 17 de junio de 2018.
Appears in Collections:(CABD) Comunicaciones congresos
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