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| Status |
Public on Sep 08, 2011 |
| Title |
Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function [visual cortex] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Autism spectrum disorders such as Rett syndrome (RTT) have been hypothesized to arise from defects in experience-dependent synapse maturation. RTT is caused by mutations in MECP2, a nuclear protein that becomes phosphorylated at S421 in response to neuronal activation. We show here that disruption of MeCP2 S421 phosphorylation in vivo results in defects in synapse development and behavior, implicating activity-dependent regulation of MeCP2 in brain development and RTT. We investigated the mechanism by which S421 phosphorylation regulates MeCP2 function and show by chromatin immunoprecipitation-sequencing that this modification occurs on MeCP2 bound across the genome. The phosphorylation of MeCP2 S421 appears not to regulate the expression of specific genes; rather, MeCP2 functions as a histone-like factor whose phosphorylation may facilitate a genome-wide response of chromatin to neuronal activity during nervous system development. We propose that RTT results in part from a loss of this experience-dependent chromatin remodeling.
Gene expression analysis of RNA isolated from P17 mouse visual cortex was performed comparing global gene expression between Wild-Type and MeCP2 S421A knock-in mice.
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| Overall design |
We isolated RNA from the visual cortex of 4 wild-type and 4 MeCP2 S421A littermate P17 Mice, and analyzed mRNA expression using the Affymetrix Mouse Gene 1.0 ST microarray platform.
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| Contributor(s) |
Cohen S, Hemberg M, Hutchinson AN, Sadacca LA, Ebert DH, Harmin DA, Greenberg RS, Zhou Z, Wetsel WC, West AE, Gabel HW, Greenberg ME |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Sep 02, 2011 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Harrison Wren Gabel |
| E-mail(s) |
[email protected]
|
| Phone |
617-512-0289
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| Organization name |
Harvard Medical School
|
| Department |
Neurobiology
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| Lab |
Michael Greenberg
|
| Street address |
7 Linden St Apt 3
|
| City |
Brookline |
| State/province |
MA |
| ZIP/Postal code |
02445 |
| Country |
USA |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE31851 |
Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function |
|
| Relations |
| BioProject |
PRJNA155261 |
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