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Mutation of MeCP2 alters transcriptional regulation of select immediate-early genes.

Publication ,  Journal Article
Su, D; Cha, YM; West, AE
Published in: Epigenetics
February 2012

Loss-of-function mutations in the methyl-DNA binding protein MeCP2 are associated with neurological dysfunction and impaired neural plasticity. However, the transcriptional changes that underlie these deficits remain poorly understood. Here, we show that mice bearing a C-terminal truncating mutation in Mecp2 (Mecp2 ( 308) ) are hypersensitive to the locomotor stimulating effects of cocaine. Furthermore, these mice have gene-specific alterations in striatal immediate-early gene (IEG) induction following cocaine administration. MeCP2 mutant mice show normal levels of baseline and cocaine-induced striatal Fos expression compared with their wild-type littermates. However, the mutant mice have enhanced cocaine-induced transcription of Junb and Arc. At the chromatin level, we find increased histone H3 acetylation at gene promoters in the Mecp2 mutant mice compared with their wild-type littermates, whereas two sites of repressive histone methylation are unchanged. Interestingly, we find that MeCP2 mutant mice show increased steady-state association of elongation-competent RNA Polymerase II (RNAP II) with the Junb and Arc promoters, whereas levels of RNAP II association at the Fos promoter are unchanged. These data reveal a gene-specific effect of MeCP2 on the recruitment of RNAP II to gene promoters that may modulate the inducibility of IEGs. In addition, our findings raise the possibility that aberrant regulation of IEGs including Junb and Arc may contribute to altered cocaine-induced neuronal and behavioral plasticity in Mecp2 mutant mice.

Duke Scholars

Published In

Epigenetics

DOI

EISSN

1559-2308

Publication Date

February 2012

Volume

7

Issue

2

Start / End Page

146 / 154

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • RNA Polymerase II
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-fos
  • Protein Binding
  • Promoter Regions, Genetic
  • Nerve Tissue Proteins
  • Mutation
  • Mice, Mutant Strains
  • Mice, Inbred C57BL
 

Citation

APA
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ICMJE
MLA
NLM
Su, D., Cha, Y. M., & West, A. E. (2012). Mutation of MeCP2 alters transcriptional regulation of select immediate-early genes. Epigenetics, 7(2), 146–154. https://doi.org/10.4161/epi.7.2.18907
Su, Dan, Young May Cha, and Anne E. West. “Mutation of MeCP2 alters transcriptional regulation of select immediate-early genes.Epigenetics 7, no. 2 (February 2012): 146–54. https://doi.org/10.4161/epi.7.2.18907.
Su D, Cha YM, West AE. Mutation of MeCP2 alters transcriptional regulation of select immediate-early genes. Epigenetics. 2012 Feb;7(2):146–54.
Su, Dan, et al. “Mutation of MeCP2 alters transcriptional regulation of select immediate-early genes.Epigenetics, vol. 7, no. 2, Feb. 2012, pp. 146–54. Pubmed, doi:10.4161/epi.7.2.18907.
Su D, Cha YM, West AE. Mutation of MeCP2 alters transcriptional regulation of select immediate-early genes. Epigenetics. 2012 Feb;7(2):146–154.

Published In

Epigenetics

DOI

EISSN

1559-2308

Publication Date

February 2012

Volume

7

Issue

2

Start / End Page

146 / 154

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • RNA Polymerase II
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-fos
  • Protein Binding
  • Promoter Regions, Genetic
  • Nerve Tissue Proteins
  • Mutation
  • Mice, Mutant Strains
  • Mice, Inbred C57BL