MeCP2 and histone deacetylases 1 and 2 in dorsal striatum collectively suppress repetitive behaviors

Melissa Mahgoub, Megumi Adachi, Kanzo Suzuki, Xihui Liu, Ege T Kavalali, Maria Chahrour, Lisa M Monteggia

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Class I histone deacetylases (HDACs) Hdac1 and Hdac2 can associate together in protein complexes with transcriptional factors such as methyl-CpG-binding protein 2 (MeCP2). Given their high degree of sequence identity, we examined whether Hdac1 and Hdac2 were functionally redundant in mature mouse brain. We demonstrate that postnatal forebrain-specific deletion of both Hdac1 and Hdac2 in mice impacts neuronal survival and results in an excessive grooming phenotype caused by dysregulation of Sap90/Psd95-associated protein 3 (Sapap3; also known as Dlgap3) in striatum. Moreover, Hdac1- and Hdac2-dependent regulation of Sapap3 expression requires MECP2, the gene involved in the pathophysiology of Rett syndrome. We show that postnatal forebrain-specific deletion of Mecp2 causes excessive grooming, which is rescued by restoring striatal Sapap3 expression. Our results provide new insight into the upstream regulation of Sapap3 and establish the essential role of striatal Hdac1, Hdac2 and MeCP2 for suppression of repetitive behaviors.

Original languageEnglish (US)
Pages (from-to)1506-1512
Number of pages7
JournalNature neuroscience
Volume19
Issue number11
DOIs
StatePublished - Oct 26 2016

ASJC Scopus subject areas

  • Neuroscience(all)

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    Mahgoub, M., Adachi, M., Suzuki, K., Liu, X., Kavalali, E. T., Chahrour, M., & Monteggia, L. M. (2016). MeCP2 and histone deacetylases 1 and 2 in dorsal striatum collectively suppress repetitive behaviors. Nature neuroscience, 19(11), 1506-1512. https://doi.org/10.1038/nn.4395