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However, the molecular mechanism of<jats:italic>ME<\/jats:italic><jats:italic>CP2<\/jats:italic>-mutation-caused RTT is less known. Here we find that MeCP2 could be SUMO-modified by the E3 ligase PIAS1 at Lys-412. MeCP2 phosphorylation (at Ser-421 and Thr-308) facilitates MeCP2 SUMOylation, and MeCP2 SUMOylation is induced by NMDA, IGF-1 and CRF in the rat brain. MeCP2 SUMOylation releases CREB from the repressor complex and enhances<jats:italic>Bdnf<\/jats:italic>mRNA expression. Several<jats:italic>MECP2<\/jats:italic>mutations identified in RTT patients show decreased MeCP2 SUMOylation. Re-expression of wild-type MeCP2 or SUMO-modified MeCP2 in<jats:italic>Mecp2<\/jats:italic>-null neurons rescues the deficits of social interaction, fear memory and LTP observed in<jats:italic>Mecp2<\/jats:italic>conditional knockout (cKO) mice. These results together reveal an important role of MeCP2 SUMOylation in social interaction, memory and synaptic plasticity, and that abnormal MeCP2 SUMOylation is implicated in RTT.<\/jats:p>","DOI":"10.1038\/ncomms10552","type":"journal-article","created":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T11:01:35Z","timestamp":1454583695000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome"],"prefix":"10.1038","volume":"7","author":[{"given":"Derek J. 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