@article{2a456a727de04f37aaa05d572fd90a7c,
title = "Genome-Wide Activity-Dependent MeCP2 Phosphorylation Regulates Nervous System Development and Function",
abstract = "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.",
author = "Sonia Cohen and Gabel, {Harrison W.} and Martin Hemberg and Hutchinson, {Ashley N.} and Sadacca, {L. Amanda} and Ebert, {Daniel H.} and Harmin, {David A.} and Greenberg, {Rachel S.} and Verdine, {Vanessa K.} and Zhaolan Zhou and Wetsel, {William C.} and West, {Anne E.} and Greenberg, {Michael E.}",
note = "Funding Information: We thank E. Griffith, P. Greer, S. Ross, N. Robinson, and Greenberg Lab members for critical reading of the manuscript; C. Chen, B. Bloodgood, E. Hong, R. Rodriguiz, J. Dodart, H. Ho, and the MRDDRC Gene Manipulation Core (M. Thompson, Y. Zhou, and H. Ye) for experimental assistance and advice. This work was supported by NIH grant 1R01NS048276 to M.E.G. A.E.W. was supported by NIH grant R01 DA022202 and March of Dimes grant 1-FY07-482; S.C. was supported by the Medical Scientist Training Program, Ruth L. Kirschstein NIH Training Grant T32CA009361, and the Department of Neurobiology Graduate Fellowship Fund at HMS; H.W.G. was supported by Damon Runyon Cancer Research Foundation Grant DRG-2048-10; D.H.E. was supported by NIH grant K08MH90306 and by the Dupont-Warren Fellowship in the Department of Psychiatry at HMS; Z.Z. was supported by NIH grant K99 NS058391. M.H. was supported by NIH grant 1R21NS070250-01A1. ",
year = "2011",
month = oct,
day = "6",
doi = "10.1016/j.neuron.2011.08.022",
language = "English",
volume = "72",
pages = "72--85",
journal = "Neuron",
issn = "0896-6273",
number = "1",
}