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Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function.

Publication ,  Journal Article
Cohen, S; Gabel, HW; Hemberg, M; Hutchinson, AN; Sadacca, LA; Ebert, DH; Harmin, DA; Greenberg, RS; Verdine, VK; Zhou, Z; Wetsel, WC; West, AE ...
Published in: Neuron
October 6, 2011
Published version (DOI) Link to item

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.

Duke Scholars

William Christopher Wetsel
Author William Christopher Wetsel Psychiatry & Behavioral Sciences, Behavioral Medicine & Neur ...
Anne Elizabeth West
Author Anne Elizabeth West Neurobiology
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Published In

Neuron

DOI

10.1016/j.neuron.2011.08.022

EISSN

1097-4199

Publication Date

October 6, 2011

Volume

72

Issue

1

Start / End Page

72 / 85

Location

United States

Related Subject Headings

  • Phosphorylation
  • Neurons
  • Neurology & Neurosurgery
  • Mice, Inbred C57BL
  • Mice
  • Methyl-CpG-Binding Protein 2
  • Genome
  • Gene Knock-In Techniques
  • Gene Expression Regulation, Developmental
  • Exploratory Behavior
 

Citation

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Cohen, S., Gabel, H. W., Hemberg, M., Hutchinson, A. N., Sadacca, L. A., Ebert, D. H., … Greenberg, M. E. (2011). Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function. Neuron, 72(1), 72–85. https://doi.org/10.1016/j.neuron.2011.08.022
Cohen, Sonia, Harrison W. Gabel, Martin Hemberg, Ashley N. Hutchinson, L Amanda Sadacca, Daniel H. Ebert, David A. Harmin, et al. “Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function.” Neuron 72, no. 1 (October 6, 2011): 72–85. https://doi.org/10.1016/j.neuron.2011.08.022.
Cohen S, Gabel HW, Hemberg M, Hutchinson AN, Sadacca LA, Ebert DH, et al. Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function. Neuron. 2011 Oct 6;72(1):72–85.
Cohen, Sonia, et al. “Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function.” Neuron, vol. 72, no. 1, Oct. 2011, pp. 72–85. Pubmed, doi:10.1016/j.neuron.2011.08.022.
Cohen S, Gabel HW, Hemberg M, Hutchinson AN, Sadacca LA, Ebert DH, Harmin DA, Greenberg RS, Verdine VK, Zhou Z, Wetsel WC, West AE, Greenberg ME. Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function. Neuron. 2011 Oct 6;72(1):72–85.
Journal cover image

Published In

Neuron

DOI

10.1016/j.neuron.2011.08.022

EISSN

1097-4199

Publication Date

October 6, 2011

Volume

72

Issue

1

Start / End Page

72 / 85

Location

United States

Related Subject Headings

  • Phosphorylation
  • Neurons
  • Neurology & Neurosurgery
  • Mice, Inbred C57BL
  • Mice
  • Methyl-CpG-Binding Protein 2
  • Genome
  • Gene Knock-In Techniques
  • Gene Expression Regulation, Developmental
  • Exploratory Behavior