Distinct gene expression profiles directed by the isoforms of the transcription factor neuron-restrictive silencer factor in human SK-N-AS neuroblastoma cells.
Neuron-restrictive silencer factor (NRSF) and its isoforms are differentially regulated in rodent models of self-sustaining status epilepticus (SSSE). NRSF isoforms regulate genes associated with SSSE, including the proconvulsant tachykinins, brain-derived neurotrophic factor and multiple ion channels. NRSF isoforms may direct distinct gene expression patterns during SSSE, and the ratio of each isoform may be a causative factor in traumatic damage to the central nervous system. Here, we analysed global gene expression changes by microarray in human SK-N-AS neuroblastoma cells following the over-expression of NRSF and a truncated isoform, HZ4. We used bioinformatics software to analyse the microarray dataset and correlated these data with epilepsy candidate gene pathways. Findings were validated by reverse transcriptase-polymerase chain reaction. We demonstrated that NRSF and HZ4 direct overlapping as well as distinct gene expression patterns, and that they differentially modulated gene expression patterns associated with epilepsy. Finally, we revealed that NRSF gene expression may be modulated by the anticonvulsant, phenytoin. We have interpreted our data to reflect altered gene expression directed by NRSF that might be relevant for SSSE.
Gillies
Stuart G
SG
Division of Human Anatomy & Cell Biology and Division of Physiology, School of Biomedical Sciences, University of Liverpool, Liverpool, UK.
Haddley
Kate
K
Vasiliou
Sylvia A
SA
Jacobson
Gregory M
GM
von Mentzer
Bengt
B
Bubb
Vivien J
VJ
Quinn
John P
JP
D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D046228:Microarray Analysis; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics* / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D000099229:RE1-Silencing Transcription Factor
D000927:Anticonvulsants; D020033:Protein Isoforms; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor