RGD Reference Report - SUMOylation of MeCP2 is essential for transcriptional repression and hippocampal synapse development. - Rat Genome Database

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SUMOylation of MeCP2 is essential for transcriptional repression and hippocampal synapse development.

Authors: Cheng, Ju  Huang, Min  Zhu, Ying  Xin, Yong-Juan  Zhao, Yun-Ke  Huang, Jian  Yu, Jian-Xiu  Zhou, Wen-Hao  Qiu, Zilong 
Citation: Cheng J, etal., J Neurochem. 2014 Mar;128(6):798-806. doi: 10.1111/jnc.12523. Epub 2013 Nov 25.
RGD ID: 12789443
Pubmed: PMID:24188180   (View Abstract at PubMed)
DOI: DOI:10.1111/jnc.12523   (Journal Full-text)

Methyl CpG binding protein 2 (MeCP2) binds to methylated DNA and acts as a transcriptional repressor. Mutations of human MECP2 gene lead to Rett syndrome, a severe neural developmental disorder. Here, we report that the MeCP2 protein can be modified by covalent linkage to small ubiquitin-like modifier (SUMO) and SUMOylation at lysine 223 is necessary for its transcriptional repression function. SUMOylation of MeCP2 is required for the recruitment of histone deacetylase complexes 1/2 complex. Mutation of MeCP2 lysine 223 to arginine abolishes its suppression of gene expression in mouse primary cortical neurons. Significantly, mutation of MeCP2 K223 site leads to developmental deficiency of rat hippocampal synapses in vitro and in vivo. Thus, the SUMOylation of MeCP2 at K223 is a critical switch for transcriptional repression and plays a crucial function in regulating synaptic development in the central nervous system.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of dendritic spine development  IMP 12789443 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mecp2  (methyl CpG binding protein 2)


Additional Information