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Distinct Gene Expression Profiles Directed by the Isoforms of the Transcription Factor Neuron-Restrictive Silencer Factor in Human SK-N-AS Neuroblastoma Cells

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Abstract

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.

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Acknowledgements

We wish to thank Dr. Graeme Sills for critical review of this manuscript. We confirm that we have read the journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. We wish to thank the MRC for studentship funding for SG and the BBSRC for funding for KH, SV, VJB and JPQ.

Conflicts of interest

None of the authors has any conflict of interest to disclose.

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Authors and Affiliations

  1. Division of Human Anatomy & Cell Biology and Division of Physiology, School of Biomedical Sciences, University of Liverpool, Liverpool, L69 3BX, UK

    Stuart G. Gillies, Kate Haddley, Sylvia A. Vasiliou, Gregory M. Jacobson, Vivien J. Bubb & John P. Quinn

  2. Pharmnovo Bio Research, Medicinaregatan 8, 413 46, Gothenburg, Sweden

    Bengt von Mentzer

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  1. Stuart G. Gillies
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  2. Kate Haddley
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  6. Vivien J. Bubb
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  7. John P. Quinn
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Correspondence to John P. Quinn.

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Gillies, S.G., Haddley, K., Vasiliou, S.A. et al. Distinct Gene Expression Profiles Directed by the Isoforms of the Transcription Factor Neuron-Restrictive Silencer Factor in Human SK-N-AS Neuroblastoma Cells. J Mol Neurosci 44, 77–90 (2011). https://doi.org/10.1007/s12031-010-9420-3

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