論文 - 詳細
| RRC ID | 45977 |
|---|---|
| 著者 | González-Aguilera C, Ikegami K, Ayuso C, de Luis A, Íñiguez M, Cabello J, Lieb JD, Askjaer P. |
| タイトル | Genome-wide analysis links emerin to neuromuscular junction activity in Caenorhabditis elegans. |
| ジャーナル | Genome Biol |
| Abstract |
BACKGROUND:Laminopathies are diseases characterized by defects in nuclear envelope structure. A well-known example is Emery-Dreifuss muscular dystrophy, which is caused by mutations in the human lamin A/C and emerin genes. While most nuclear envelope proteins are ubiquitously expressed, laminopathies often affect only a subset of tissues. The molecular mechanisms underlying these tissue-specific manifestations remain elusive. We hypothesize that different functional subclasses of genes might be differentially affected by defects in specific nuclear envelope components. RESULTS:Here we determine genome-wide DNA association profiles of two nuclear envelope components, lamin/LMN-1 and emerin/EMR-1 in adult Caenorhabditis elegans. Although both proteins bind to transcriptionally inactive regions of the genome, EMR-1 is enriched at genes involved in muscle and neuronal function. Deletion of either EMR-1 or LEM-2, another integral envelope protein, causes local changes in nuclear architecture as evidenced by altered association between DNA and LMN-1. Transcriptome analyses reveal that EMR-1 and LEM-2 are associated with gene repression, particularly of genes implicated in muscle and nervous system function. We demonstrate that emr-1, but not lem-2, mutants are sensitive to the cholinesterase inhibitor aldicarb, indicating altered activity at neuromuscular junctions. CONCLUSIONS:We identify a class of elements that bind EMR-1 but do not associate with LMN-1, and these are enriched for muscle and neuronal genes. Our data support a redundant function of EMR-1 and LEM-2 in chromatin anchoring to the nuclear envelope and gene repression. We demonstrate a specific role of EMR-1 in neuromuscular junction activity that may contribute to Emery-Dreifuss muscular dystrophy in humans. |
| 巻・号 | 15(2) |
| ページ | R21 |
| 公開日 | 2014-2-3 |
| DOI | 10.1186/gb-2014-15-2-r21 |
| PII | gb-2014-15-2-r21 |
| PMID | 24490688 |
| PMC | PMC4053756 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics* Cell Cycle Proteins Chromatin Genome-Wide Association Study* Humans Lamin Type A / genetics Membrane Proteins / genetics* Muscular Dystrophy, Emery-Dreifuss / genetics* Muscular Dystrophy, Emery-Dreifuss / pathology Mutation Neuromuscular Junction / genetics Nuclear Envelope / genetics* Nuclear Proteins / genetics* |
| IF | 10.806 |
| 引用数 | 31 |
| WOS 分野 | BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY |
| リソース情報 | |
| 線虫 | tm1582 |