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

Publication ,  Journal Article
Chen, WG; Chang, Q; Lin, Y; Meissner, A; West, AE; Griffith, EC; Jaenisch, R; Greenberg, ME
Published in: Science
October 31, 2003

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.

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Published In

Science

DOI

EISSN

1095-9203

Publication Date

October 31, 2003

Volume

302

Issue

5646

Start / End Page

885 / 889

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Rett Syndrome
  • Repressor Proteins
  • Rats
  • Promoter Regions, Genetic
  • Precipitin Tests
  • Potassium Chloride
  • Phosphorylation
  • Neurons
  • Mice, Knockout
 

Citation

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Chen, W. G., Chang, Q., Lin, Y., Meissner, A., West, A. E., Griffith, E. C., … Greenberg, M. E. (2003). Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science, 302(5646), 885–889. https://doi.org/10.1126/science.1086446
Chen, Wen G., Qiang Chang, Yingxi Lin, Alexander Meissner, Anne E. West, Eric C. Griffith, Rudolf Jaenisch, and Michael E. Greenberg. “Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2.Science 302, no. 5646 (October 31, 2003): 885–89. https://doi.org/10.1126/science.1086446.
Chen WG, Chang Q, Lin Y, Meissner A, West AE, Griffith EC, et al. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science. 2003 Oct 31;302(5646):885–9.
Chen, Wen G., et al. “Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2.Science, vol. 302, no. 5646, Oct. 2003, pp. 885–89. Pubmed, doi:10.1126/science.1086446.
Chen WG, Chang Q, Lin Y, Meissner A, West AE, Griffith EC, Jaenisch R, Greenberg ME. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science. 2003 Oct 31;302(5646):885–889.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

October 31, 2003

Volume

302

Issue

5646

Start / End Page

885 / 889

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Rett Syndrome
  • Repressor Proteins
  • Rats
  • Promoter Regions, Genetic
  • Precipitin Tests
  • Potassium Chloride
  • Phosphorylation
  • Neurons
  • Mice, Knockout