SOX11 target genes: implications for neurogenesis and neuropsychiatric illness
Li Sha
Medical Genetics, Institute for Genetics and Molecular Medicine, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh, UK
Search for more papers by this authorRob Kitchen
Medical Genetics, Institute for Genetics and Molecular Medicine, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh, UK
School of Physics, University of Edinburgh, Edinburgh, UK
Search for more papers by this authorDavid Porteous
Medical Genetics, Institute for Genetics and Molecular Medicine, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh, UK
Search for more papers by this authorDouglas Blackwood
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK
Search for more papers by this authorWalter Muir
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK
Deceased.
Search for more papers by this authorCorresponding Author
Benjamin Pickard
Medical Genetics, Institute for Genetics and Molecular Medicine, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh, UK
Strathclyde Institute of Pharmacy and Biomedical Sciences, Centre for Neuroscience, University of Strathclyde, Glasgow, UK
Benjamin Pickard, Strathclyde Institute of Pharmacy and Biomedical Sciences, The Andrew Hamnett Wing, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.Tel: +44 141 548 4572;Fax: +44 141 552 2562;E-mail: [email protected]Search for more papers by this authorLi Sha
Medical Genetics, Institute for Genetics and Molecular Medicine, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh, UK
Search for more papers by this authorRob Kitchen
Medical Genetics, Institute for Genetics and Molecular Medicine, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh, UK
School of Physics, University of Edinburgh, Edinburgh, UK
Search for more papers by this authorDavid Porteous
Medical Genetics, Institute for Genetics and Molecular Medicine, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh, UK
Search for more papers by this authorDouglas Blackwood
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK
Search for more papers by this authorWalter Muir
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK
Deceased.
Search for more papers by this authorCorresponding Author
Benjamin Pickard
Medical Genetics, Institute for Genetics and Molecular Medicine, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh, UK
Strathclyde Institute of Pharmacy and Biomedical Sciences, Centre for Neuroscience, University of Strathclyde, Glasgow, UK
Benjamin Pickard, Strathclyde Institute of Pharmacy and Biomedical Sciences, The Andrew Hamnett Wing, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.Tel: +44 141 548 4572;Fax: +44 141 552 2562;E-mail: [email protected]Search for more papers by this authorAbstract
Sha L, Kitchen R, Porteous D, Blackwood D, Muir W, Pickard B. SOX11 target genes: implications for neurogenesis and neuropsychiatric illness.
Objective: Deficits in adult and embryonic neurogenesis have been linked with neurological and psychiatric disorders, so it is important to understand the molecular mechanisms underlying this process. SOX11 is a transcription factor known to play a critical role in the regulation of the neuronal and glial differentiation stage of neurogenesis, so we hypothesised that the identification of its target genes would reveal underlying biological processes relevant to disease.
Methods: SOX11 protein was over-expressed in HEK293 cells and transcriptional changes assessed by microarray analysis. Selected candidate genes were further tested for SOX11 activation in quantitative reverse transcriptase PCR studies of HEK293 cells and Western analysis of SH-SY5Y cells.
Results: Regulated genes included a previously established SOX11 target, known markers of neurogenesis, as well as several genes implicated in neuropsychiatric disorders. Immunofluorescence localised several of the genes within the proliferative subgranular zone of the hippocampus. We observed multiple histone and zinc finger genes regulated by SOX11, many of which were located in two clusters on chromosomes 6 and 19. The chromosome 6 cluster lies within a region of the genome showing the strongest genetic association with schizophrenia.
Conclusion: SOX11 appears to regulate a complex programme of chromatin remodelling and downstream gene expression changes to achieve a mature neuronal phenotype. SOX11 target genes are shown to be involved in neurodevelopmental processes important in health and, potentially, disease.
Supporting Information
Supporting Information
The following Supporting information is available for this article:
Table S1. 932 genes significant by SAM – Significance analysis of microarrays
Table S2. PCR primers used in validation and timecourse QPCR assay. Primers were designed using PRIMER3 [http://workbench.sdsc.edu]. Specificity of all primers was checked by Blast and BLAT analyses http://www.ncbi.nlm.nih.gov/Blast.cgi
Table S3. Significantly (SAM) regulated genes, shown in order, that are found within clusters on chromosomes 6 and 19. The two genes highlighted in bold show downregulation, the rest are upregulated. Histones and zinc finger proteins comprise the majority of the list
Additional Supporting information may be found in the online version of this article.
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| ACN_583_sm_ts1_ts3.doc1.3 MB | Supporting info item |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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