Publication Date:
2003-11-01
Description:
Mutations in MeCP2, which encodes a protein that has been proposed to function as a global transcriptional repressor, are the cause of Rett syndrome (RT T), an X-linked progressive neurological disorder. Although the selective inactivation of MeCP2 in neurons is sufficient to confer a Rett-like phenotype in mice, the specific functions of MeCP2 in postmitotic neurons are not known. We find that MeCP2 binds selectively to BDNF promoter III and functions to repress expression of the BDNF gene. Membrane depolarization triggers the calcium-dependent phosphorylation and release of MeCP2 from BDNF promoter III, thereby facilitating transcription. These studies indicate that MeCP2 plays a key role in the control of neuronal activity-dependent gene regulation and suggest that the deregulation of this process may underlie the pathology of RT T.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Wen G -- Chang, Qiang -- Lin, Yingxi -- Meissner, Alexander -- West, Anne E -- Griffith, Eric C -- Jaenisch, Rudolf -- Greenberg, Michael E -- HD 18655/HD/NICHD NIH HHS/ -- NS28829/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 31;302(5646):885-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14593183" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Brain-Derived Neurotrophic Factor/*genetics
;
Calcium/*metabolism
;
Cell Membrane/physiology
;
Cells, Cultured
;
*Chromosomal Proteins, Non-Histone
;
Cloning, Molecular
;
CpG Islands
;
DNA Methylation
;
DNA-Binding Proteins/*metabolism
;
Electrophoretic Mobility Shift Assay
;
*Gene Expression Regulation
;
Gene Silencing
;
Histones/metabolism
;
Methyl-CpG-Binding Protein 2
;
Methylation
;
Mice
;
Mice, Knockout
;
Neurons/metabolism/physiology
;
Phosphorylation
;
Potassium Chloride/pharmacology
;
Precipitin Tests
;
Promoter Regions, Genetic
;
Rats
;
*Repressor Proteins
;
Rett Syndrome/genetics
;
*Transcription, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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