The protocadherins, <it>PCDHB1 </it>and <it>PCDH7</it>, are regulated by MeCP2 in neuronal cells and brain tissues: implication for pathogenesis of Rett syndrome
<p>Abstract</p> <p>Background</p> <p>Rett syndrome is a neurodevelopmental and autistic disease caused by mutations of <it>Methyl-CpG-binding protein 2 </it>(<it>MECP2</it>) gene. MeCP2 protein is mainly expressed in neurons and binds to methylat...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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BMC
2011-08-01
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| Series: | BMC Neuroscience |
| Online Access: | http://www.biomedcentral.com/1471-2202/12/81 |
| _version_ | 1818756899318792192 |
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| author | Nakagawa Takayuki Kudo Shinichi Takahashi Kenichiro Endoh Kazushi Goto Yu-ichi Itoh Masayuki Soutome Masaki Hirasawa Takae Miyake Kunio Yokoi Sana Taira Takahiro Inazawa Johji Kubota Takeo |
| author_facet | Nakagawa Takayuki Kudo Shinichi Takahashi Kenichiro Endoh Kazushi Goto Yu-ichi Itoh Masayuki Soutome Masaki Hirasawa Takae Miyake Kunio Yokoi Sana Taira Takahiro Inazawa Johji Kubota Takeo |
| author_sort | Nakagawa Takayuki |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Rett syndrome is a neurodevelopmental and autistic disease caused by mutations of <it>Methyl-CpG-binding protein 2 </it>(<it>MECP2</it>) gene. MeCP2 protein is mainly expressed in neurons and binds to methylated gene promoters to suppress their expression, indicating that Rett syndrome is caused by the deregulation of target genes in neurons. However, it is likely that there are more unidentified neuronal MeCP2-targets associated with the neurological features of RTT.</p> <p>Results</p> <p>Using a genome-microarray approach, we found 22 genomic regions that contain sites potentially regulated by MeCP2 based on the features of MeCP2 binding, DNA methylation, and repressive histone modification in human cell lines. Within these regions, Chromatin immunoprecipitation (ChIP) analysis revealed that MeCP2 binds to the upstream regions of the protocadherin genes <it>PCDHB1 </it>and <it>PCDH7 </it>in human neuroblastoma SH-SY5Y cells. PCDHB1 and PCDH7 promoter activities were down-regulated by MeCP2, but not by MBD-deleted MeCP2. These gene expression were up-regulated following MeCP2 reduction with siRNA in SH-SY5Y cells and in the brains of <it>Mecp2</it>-null mice. Furthermore, <it>PCDHB1 </it>was up-regulated in postmortem brains from Rett syndrome patients.</p> <p>Conclusions</p> <p>We identified MeCP2 target genes that encode neuronal adhesion molecules using ChIP-on-BAC array approach. Since these protocadherin genes are generally essential for brain development, aberrant regulation of these molecules may contribute to the pathogenesis of the neurological features observed in Rett syndrome.</p> |
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| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-12-18T06:02:22Z |
| publishDate | 2011-08-01 |
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| spelling | doaj.art-3d02ce6a80954263aa0fd6bcb5e631962022-12-21T21:18:39ZengBMCBMC Neuroscience1471-22022011-08-011218110.1186/1471-2202-12-81The protocadherins, <it>PCDHB1 </it>and <it>PCDH7</it>, are regulated by MeCP2 in neuronal cells and brain tissues: implication for pathogenesis of Rett syndromeNakagawa TakayukiKudo ShinichiTakahashi KenichiroEndoh KazushiGoto Yu-ichiItoh MasayukiSoutome MasakiHirasawa TakaeMiyake KunioYokoi SanaTaira TakahiroInazawa JohjiKubota Takeo<p>Abstract</p> <p>Background</p> <p>Rett syndrome is a neurodevelopmental and autistic disease caused by mutations of <it>Methyl-CpG-binding protein 2 </it>(<it>MECP2</it>) gene. MeCP2 protein is mainly expressed in neurons and binds to methylated gene promoters to suppress their expression, indicating that Rett syndrome is caused by the deregulation of target genes in neurons. However, it is likely that there are more unidentified neuronal MeCP2-targets associated with the neurological features of RTT.</p> <p>Results</p> <p>Using a genome-microarray approach, we found 22 genomic regions that contain sites potentially regulated by MeCP2 based on the features of MeCP2 binding, DNA methylation, and repressive histone modification in human cell lines. Within these regions, Chromatin immunoprecipitation (ChIP) analysis revealed that MeCP2 binds to the upstream regions of the protocadherin genes <it>PCDHB1 </it>and <it>PCDH7 </it>in human neuroblastoma SH-SY5Y cells. PCDHB1 and PCDH7 promoter activities were down-regulated by MeCP2, but not by MBD-deleted MeCP2. These gene expression were up-regulated following MeCP2 reduction with siRNA in SH-SY5Y cells and in the brains of <it>Mecp2</it>-null mice. Furthermore, <it>PCDHB1 </it>was up-regulated in postmortem brains from Rett syndrome patients.</p> <p>Conclusions</p> <p>We identified MeCP2 target genes that encode neuronal adhesion molecules using ChIP-on-BAC array approach. Since these protocadherin genes are generally essential for brain development, aberrant regulation of these molecules may contribute to the pathogenesis of the neurological features observed in Rett syndrome.</p>http://www.biomedcentral.com/1471-2202/12/81 |
| spellingShingle | Nakagawa Takayuki Kudo Shinichi Takahashi Kenichiro Endoh Kazushi Goto Yu-ichi Itoh Masayuki Soutome Masaki Hirasawa Takae Miyake Kunio Yokoi Sana Taira Takahiro Inazawa Johji Kubota Takeo The protocadherins, <it>PCDHB1 </it>and <it>PCDH7</it>, are regulated by MeCP2 in neuronal cells and brain tissues: implication for pathogenesis of Rett syndrome BMC Neuroscience |
| title | The protocadherins, <it>PCDHB1 </it>and <it>PCDH7</it>, are regulated by MeCP2 in neuronal cells and brain tissues: implication for pathogenesis of Rett syndrome |
| title_full | The protocadherins, <it>PCDHB1 </it>and <it>PCDH7</it>, are regulated by MeCP2 in neuronal cells and brain tissues: implication for pathogenesis of Rett syndrome |
| title_fullStr | The protocadherins, <it>PCDHB1 </it>and <it>PCDH7</it>, are regulated by MeCP2 in neuronal cells and brain tissues: implication for pathogenesis of Rett syndrome |
| title_full_unstemmed | The protocadherins, <it>PCDHB1 </it>and <it>PCDH7</it>, are regulated by MeCP2 in neuronal cells and brain tissues: implication for pathogenesis of Rett syndrome |
| title_short | The protocadherins, <it>PCDHB1 </it>and <it>PCDH7</it>, are regulated by MeCP2 in neuronal cells and brain tissues: implication for pathogenesis of Rett syndrome |
| title_sort | protocadherins it pcdhb1 it and it pcdh7 it are regulated by mecp2 in neuronal cells and brain tissues implication for pathogenesis of rett syndrome |
| url | http://www.biomedcentral.com/1471-2202/12/81 |
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