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DNA methyltransferase I regulates reelin mRNA expression in mouse primary cortical cultures.

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Title: DNA methyltransferase I regulates reelin mRNA expression in mouse primary cortical cultures.
Authors: Jai Sung Noh1 Jgrayson@psych.uic.edu, Sharma, Rajiv P.2, Veldic, Mann2, Salvacion, Alain A.2, Xiaomei Jia2, Ying Chen2, Costa, Erminio2
Source: Proceedings of the National Academy of Sciences of the United States of America. 2/1/2005, Vol. 102 Issue 5, p1749-1754. 6p.
Subjects: Methyltransferases, Methionine, Messenger RNA, Nervous system, Neurons, Gene expression, Genetic regulation
Abstract: The polygenic nature of complex psychiatric disorders suggests a common pathway that may be involved in the down-regulation of multiple genes through an epigenetic mechanism. To investigate the role of methylation in down-regulating the expression of mRNAs that may be associated with the schizophrenia phenotype, we have adopted a cell-culture model amenable to this line of investigation. We have administered methionine (2 mM) to primary cultures of cortical neurons prepared from embryonic day 16 mice and show that this treatment down-regulated reelin and glutamic acid decarboxylase 67 (GAD67) mRNA expression but not that corresponding to neuron-specific enolase mRNA. Moreover, methionine increased methylation of the reelin promoter, suggesting a possible mechanism for the observed change. These cultures contain a mixed population of neurons and glia. Approximately 83% of the neurons are GABAergic based on GAD immunoreactivity, and these neurons coexpress high levels of reelin and DNA methyltransferase (Dnmt) 1 immunoreactivity. To examine whether Dnmt1 regulates reelin gene expression, we used an antisense approach to reduce (knock down) Dnmt1 expression. The reduced Dnmt1 mRNA and protein were accompanied by increased reelin mRNA expression. More importantly, the Dnmt1 knockdown blocked the methionine-induced reelin and GAD67 mRNA down-regulation. These data support the hypothesis that the reduced amounts of reelin and GAD67 mRNAs documented in postmortem schizophrenia brain may be the consequence of a Dnmt1-mediated hypermethylation of the corresponding promoters. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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PubTypeId: academicJournal
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  Data: DNA methyltransferase I regulates reelin mRNA expression in mouse primary cortical cultures.
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  Data: <searchLink fieldCode="AR" term="%22Jai+Sung+Noh%22">Jai Sung Noh</searchLink><relatesTo>1</relatesTo><i> Jgrayson@psych.uic.edu</i><br /><searchLink fieldCode="AR" term="%22Sharma%2C+Rajiv+P%2E%22">Sharma, Rajiv P.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Veldic%2C+Mann%22">Veldic, Mann</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Salvacion%2C+Alain+A%2E%22">Salvacion, Alain A.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Xiaomei+Jia%22">Xiaomei Jia</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Ying+Chen%22">Ying Chen</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Costa%2C+Erminio%22">Costa, Erminio</searchLink><relatesTo>2</relatesTo>
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  Data: <searchLink fieldCode="DE" term="%22Methyltransferases%22">Methyltransferases</searchLink><br /><searchLink fieldCode="DE" term="%22Methionine%22">Methionine</searchLink><br /><searchLink fieldCode="DE" term="%22Messenger+RNA%22">Messenger RNA</searchLink><br /><searchLink fieldCode="DE" term="%22Nervous+system%22">Nervous system</searchLink><br /><searchLink fieldCode="DE" term="%22Neurons%22">Neurons</searchLink><br /><searchLink fieldCode="DE" term="%22Gene+expression%22">Gene expression</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+regulation%22">Genetic regulation</searchLink>
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  Data: The polygenic nature of complex psychiatric disorders suggests a common pathway that may be involved in the down-regulation of multiple genes through an epigenetic mechanism. To investigate the role of methylation in down-regulating the expression of mRNAs that may be associated with the schizophrenia phenotype, we have adopted a cell-culture model amenable to this line of investigation. We have administered methionine (2 mM) to primary cultures of cortical neurons prepared from embryonic day 16 mice and show that this treatment down-regulated reelin and glutamic acid decarboxylase 67 (GAD67) mRNA expression but not that corresponding to neuron-specific enolase mRNA. Moreover, methionine increased methylation of the reelin promoter, suggesting a possible mechanism for the observed change. These cultures contain a mixed population of neurons and glia. Approximately 83% of the neurons are GABAergic based on GAD immunoreactivity, and these neurons coexpress high levels of reelin and DNA methyltransferase (Dnmt) 1 immunoreactivity. To examine whether Dnmt1 regulates reelin gene expression, we used an antisense approach to reduce (knock down) Dnmt1 expression. The reduced Dnmt1 mRNA and protein were accompanied by increased reelin mRNA expression. More importantly, the Dnmt1 knockdown blocked the methionine-induced reelin and GAD67 mRNA down-regulation. These data support the hypothesis that the reduced amounts of reelin and GAD67 mRNAs documented in postmortem schizophrenia brain may be the consequence of a Dnmt1-mediated hypermethylation of the corresponding promoters. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1073/pnas.0409648102
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      – Code: eng
        Text: English
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        PageCount: 6
        StartPage: 1749
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      – SubjectFull: Methyltransferases
        Type: general
      – SubjectFull: Methionine
        Type: general
      – SubjectFull: Messenger RNA
        Type: general
      – SubjectFull: Nervous system
        Type: general
      – SubjectFull: Neurons
        Type: general
      – SubjectFull: Gene expression
        Type: general
      – SubjectFull: Genetic regulation
        Type: general
    Titles:
      – TitleFull: DNA methyltransferase I regulates reelin mRNA expression in mouse primary cortical cultures.
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          Name:
            NameFull: Jai Sung Noh
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            NameFull: Sharma, Rajiv P.
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            NameFull: Veldic, Mann
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            NameFull: Xiaomei Jia
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            NameFull: Ying Chen
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            NameFull: Costa, Erminio
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            – D: 01
              M: 02
              Text: 2/1/2005
              Type: published
              Y: 2005
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              Value: 102
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            – TitleFull: Proceedings of the National Academy of Sciences of the United States of America
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