Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain
Background: The Rett Syndrome (RTT) brain displays regional histopathology and volumetric reduction, with frontal cortex showing such abnormalities, whereas the occipital cortex is relatively less affected. Results: Using microarrays and quantitative PCR, the mRNA expression profiles of these two ne...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BioMed Central Ltd
2010
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| Online Access: | http://hdl.handle.net/1721.1/59015 |
| _version_ | 1811079387619000320 |
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| author | Gibson, Joanne H Slobedman, Barry Kn, Harikrishnan Williamson, Sarah L Minchenko, Dimitri El-Osta, Assam Stern, Joshua L Christodoulou, John |
| author2 | Picower Institute for Learning and Memory |
| author_facet | Picower Institute for Learning and Memory Gibson, Joanne H Slobedman, Barry Kn, Harikrishnan Williamson, Sarah L Minchenko, Dimitri El-Osta, Assam Stern, Joshua L Christodoulou, John |
| author_sort | Gibson, Joanne H |
| collection | MIT |
| description | Background: The Rett Syndrome (RTT) brain displays regional histopathology and volumetric reduction, with frontal cortex showing such abnormalities, whereas the occipital cortex is relatively less affected. Results: Using microarrays and quantitative PCR, the mRNA expression profiles of these two neuroanatomical regions were compared in postmortem brain tissue from RTT patients and normal controls. A subset of genes was differentially expressed in the frontal cortex of RTT brains, some of which are known to be associated with neurological disorders (clusterin and cytochrome c oxidase subunit 1) or are involved in synaptic vesicle cycling (dynamin 1). RNAi-mediated knockdown of MeCP2 in vitro, followed by further expression analysis demonstrated that the same direction of abnormal expression was recapitulated with MeCP2 knockdown, which for cytochrome c oxidase subunit 1 was associated with a functional respiratory chain defect. Chromatin immunoprecipitation (ChIP) analysis showed that MeCP2 associated with the promoter regions of some of these genes suggesting that loss of MeCP2 function may be responsible for their overexpression. Conclusions: This study has shed more light on the subset of aberrantly expressed genes that result from MECP2 mutations. The mitochondrion has long been implicated in the pathogenesis of RTT, however it has not been at the forefront of RTT research interest since the discovery of MECP2 mutations. The functional consequence of the underexpression of cytochrome c oxidase subunit 1 indicates that this is an area that should be revisited. |
| first_indexed | 2024-09-23T11:14:13Z |
| format | Article |
| id | mit-1721.1/59015 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:14:13Z |
| publishDate | 2010 |
| publisher | BioMed Central Ltd |
| record_format | dspace |
| spelling | mit-1721.1/590152022-09-27T18:03:43Z Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain Gibson, Joanne H Slobedman, Barry Kn, Harikrishnan Williamson, Sarah L Minchenko, Dimitri El-Osta, Assam Stern, Joshua L Christodoulou, John Picower Institute for Learning and Memory Gibson, Joanne H. Background: The Rett Syndrome (RTT) brain displays regional histopathology and volumetric reduction, with frontal cortex showing such abnormalities, whereas the occipital cortex is relatively less affected. Results: Using microarrays and quantitative PCR, the mRNA expression profiles of these two neuroanatomical regions were compared in postmortem brain tissue from RTT patients and normal controls. A subset of genes was differentially expressed in the frontal cortex of RTT brains, some of which are known to be associated with neurological disorders (clusterin and cytochrome c oxidase subunit 1) or are involved in synaptic vesicle cycling (dynamin 1). RNAi-mediated knockdown of MeCP2 in vitro, followed by further expression analysis demonstrated that the same direction of abnormal expression was recapitulated with MeCP2 knockdown, which for cytochrome c oxidase subunit 1 was associated with a functional respiratory chain defect. Chromatin immunoprecipitation (ChIP) analysis showed that MeCP2 associated with the promoter regions of some of these genes suggesting that loss of MeCP2 function may be responsible for their overexpression. Conclusions: This study has shed more light on the subset of aberrantly expressed genes that result from MECP2 mutations. The mitochondrion has long been implicated in the pathogenesis of RTT, however it has not been at the forefront of RTT research interest since the discovery of MECP2 mutations. The functional consequence of the underexpression of cytochrome c oxidase subunit 1 indicates that this is an area that should be revisited. National Health and Medical Research Council (Australia) (NHMRC) (project grant 185202) National Health and Medical Research Council (Australia) (NHMRC) (project grant 346603) 2010-10-12T14:25:16Z 2010-10-12T14:25:16Z 2010-04 2009-09 2010-09-03T16:06:58Z Article http://purl.org/eprint/type/JournalArticle 1471-2202 http://hdl.handle.net/1721.1/59015 BMC Neuroscience. 2010 Apr 26;11(1):53 20420693 en http://dx.doi.org/10.1186/1471-2202-11-53 BMC Neuroscience Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 Gibson et al.; licensee BioMed Central Ltd. application/pdf BioMed Central Ltd BioMed Central Ltd |
| spellingShingle | Gibson, Joanne H Slobedman, Barry Kn, Harikrishnan Williamson, Sarah L Minchenko, Dimitri El-Osta, Assam Stern, Joshua L Christodoulou, John Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain |
| title | Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain |
| title_full | Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain |
| title_fullStr | Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain |
| title_full_unstemmed | Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain |
| title_short | Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain |
| title_sort | downstream targets of methyl cpg binding protein 2 and their abnormal expression in the frontal cortex of the human rett syndrome brain |
| url | http://hdl.handle.net/1721.1/59015 |
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