• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

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.

Pubmed ID: 21982370

Authors

  • 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

Journal

Neuron

Publication Data

October 6, 2011

Associated Grants

  • Agency: NINDS NIH HHS, Id: 1R01NS048276
  • Agency: NINDS NIH HHS, Id: 1R21NS070250-01A1
  • Agency: NIMH NIH HHS, Id: K08MH90306
  • Agency: NINDS NIH HHS, Id: K99 NS058391
  • Agency: NINDS NIH HHS, Id: R00 NS058391
  • Agency: NIDA NIH HHS, Id: R01 DA022202
  • Agency: NIDA NIH HHS, Id: R01 DA022202
  • Agency: NINDS NIH HHS, Id: R01 NS048276
  • Agency: NINDS NIH HHS, Id: R01 NS048276-01
  • Agency: NINDS NIH HHS, Id: R01 NS048276-02
  • Agency: NINDS NIH HHS, Id: R01 NS048276-03
  • Agency: NINDS NIH HHS, Id: R01 NS048276-04
  • Agency: NINDS NIH HHS, Id: R01 NS048276-05
  • Agency: NINDS NIH HHS, Id: R01 NS048276-06
  • Agency: NINDS NIH HHS, Id: R01 NS048276-06S1
  • Agency: NINDS NIH HHS, Id: R01 NS048276-07
  • Agency: NINDS NIH HHS, Id: R01 NS048276-08
  • Agency: NIGMS NIH HHS, Id: T32 GM007753
  • Agency: NCI NIH HHS, Id: T32CA009361

Mesh Terms

  • Animals
  • Brain
  • Chromatin
  • Chromatin Immunoprecipitation
  • Dendrites
  • Exploratory Behavior
  • Gene Expression Regulation, Developmental
  • Gene Knock-In Techniques
  • Genome
  • Methyl-CpG-Binding Protein 2
  • Mice
  • Mice, Inbred C57BL
  • Neurons
  • Phosphorylation