Genome-Wide Activity-Dependent MeCP2 Phosphorylation Regulates Nervous System Development and Function

被引：223

作者：

Cohen, Sonia ^{[1
]}

Gabel, Harrison W. ^{[1
]}

Hemberg, Martin ^{[2
]}

Hutchinson, Ashley N. ^{[3
]}

Sadacca, L. Amanda ^{[1
]}

Ebert, Daniel H. ^{[1
]}

Harmin, David A. ^{[1
]}

Greenberg, Rachel S. ^{[1
]}

Verdine, Vanessa K. ^{[1
]}

Zhou, Zhaolan ^{[1
]}

Wetsel, William C. ^{[3
]}

West, Anne E. ^{[3
]}

Greenberg, Michael E. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA

[2] Childrens Hosp Boston, Dept Ophthalmol, Boston, MA 02115 USA

[3] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA

来源：

NEURON | 2011年 / 72卷 / 01期

关键词：

RETT-SYNDROME; MOUSE MODEL; BDNF TRANSCRIPTION; PYRAMIDAL NEURONS; DENDRITIC GROWTH; BINDING-SITES; HISTONE H1; CHROMATIN; PROTEIN; BRAIN;

D O I：

10.1016/j.neuron.2011.08.022

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Autism spectrum disorders such as Rett syndrome (RTT) have been hypothesized to arise from defects in experience-dependent synapse maturation. FIT 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.

引用

页码：72 / 85

页数：14

共 41 条

[1] Neuropathology of Rett syndrome [J].