Genome-wide analysis links emerin to neuromuscular junction activity in Caenorhabditis elegans.
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.
Cristina
C
González-Aguilera
Kohta
K
Ikegami
Cristina
C
Ayuso
Alberto
A
de Luis
María
M
Íñiguez
Juan
J
Cabello
Jason D
JD
Lieb
Peter
P
Askjaer
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D002843:Chromatin; D055106:Genome-Wide Association Study; D006801:Humans; D034904:Lamin Type A / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009469:Neuromuscular Junction / Q000235:genetics; D009685:Nuclear Envelope / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; C573699:EMR-1 protein, C elegans; C494847:LMNA protein, human; D034904:Lamin Type A; D008565:Membrane Proteins; D009687:Nuclear Proteins; C092710:emerin; C485768:lem-2 protein, C elegans