Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2.

Published

Journal Article

Mutations in MeCP2, which encodes a protein that has been proposed to function as a global transcriptional repressor, are the cause of Rett syndrome (RT T), an X-linked progressive neurological disorder. Although the selective inactivation of MeCP2 in neurons is sufficient to confer a Rett-like phenotype in mice, the specific functions of MeCP2 in postmitotic neurons are not known. We find that MeCP2 binds selectively to BDNF promoter III and functions to repress expression of the BDNF gene. Membrane depolarization triggers the calcium-dependent phosphorylation and release of MeCP2 from BDNF promoter III, thereby facilitating transcription. These studies indicate that MeCP2 plays a key role in the control of neuronal activity-dependent gene regulation and suggest that the deregulation of this process may underlie the pathology of RT T.

Full Text

Duke Authors

Cited Authors

  • Chen, WG; Chang, Q; Lin, Y; Meissner, A; West, AE; Griffith, EC; Jaenisch, R; Greenberg, ME

Published Date

  • October 1, 2003

Published In

Volume / Issue

  • 302 / 5646

Start / End Page

  • 885 - 889

PubMed ID

  • 14593183

Pubmed Central ID

  • 14593183

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.1086446

Language

  • eng