CpG methylation, chromatin structure and gene silencing—a three‐way connection

CpG methylation, chromatin structure and gene silencing—a three‐way connection The three‐way connection between DNA methylation, gene activity and chromatin structure has been known for almost two decades. Nevertheless, the molecular link between methyl groups on the DNA and the positioning of nucleosomes to form an inactive chromatin configuration was missing. This review discusses recent experimental data that may, for the first time, shed light on this molecular link. MeCP2, which is a known methylcytosine‐binding protein, has been shown to possess a transcriptional repressor domain (TRD) that binds the corepressor mSin3A. This corepressor protein constitutes the core of a multiprotein complex that includes histone deacetylases (HDAC1 and HDAC2). Transfection and injection experiments with methylated constructs have revealed that the silenced state of a methylated gene, which is associated with a deacetylated nucleosomal structure, could be relieved by the deacetylase inhibitor, trichostatin A. Thus, methylation plays a pivotal role in establishing and maintaining an inactive state of a gene by rendering the chromatin structure inaccessible to the transcription machinery. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The EMBO Journal Wiley

CpG methylation, chromatin structure and gene silencing—a three‐way connection

The EMBO Journal, Volume 17 (17) – Jan 1, 1998

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Publisher
Wiley
Copyright
Copyright © 2013 Wiley Periodicals, Inc
ISSN
0261-4189
eISSN
1460-2075
DOI
10.1093/emboj/17.17.4905
Publisher site
See Article on Publisher Site

Abstract

The three‐way connection between DNA methylation, gene activity and chromatin structure has been known for almost two decades. Nevertheless, the molecular link between methyl groups on the DNA and the positioning of nucleosomes to form an inactive chromatin configuration was missing. This review discusses recent experimental data that may, for the first time, shed light on this molecular link. MeCP2, which is a known methylcytosine‐binding protein, has been shown to possess a transcriptional repressor domain (TRD) that binds the corepressor mSin3A. This corepressor protein constitutes the core of a multiprotein complex that includes histone deacetylases (HDAC1 and HDAC2). Transfection and injection experiments with methylated constructs have revealed that the silenced state of a methylated gene, which is associated with a deacetylated nucleosomal structure, could be relieved by the deacetylase inhibitor, trichostatin A. Thus, methylation plays a pivotal role in establishing and maintaining an inactive state of a gene by rendering the chromatin structure inaccessible to the transcription machinery.

Journal

The EMBO JournalWiley

Published: Jan 1, 1998

Keywords: ; ; ;

References

  • DNA methylation and development
    Cedar, H; Razin, A
  • DNA methylation directs a time‐dependent repression of transcription initiation
    Kass, SU; Landsberger, N; Wolffe, AP
  • Involvement of histone H1 in the organization of the nucleosome and of the salt‐dependent superstructure of chromatin
    Thoma, F; Koller, T; Klug, A
  • Histone acetylation: influence on transcription, nucleosome mobility and positioning and linker histone‐dependent transcriptional repression
    Ura, K; Kurumizaka, H; Dimitrov, S; Almouzni, G; Wolffe, AP

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