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Histone methylation-dependent mechanisms impose ligand dependency for gene activation by nuclear receptors.

Cell | Feb 9, 2007

http://www.ncbi.nlm.nih.gov/pubmed/17289570

Nuclear receptors undergo ligand-dependent conformational changes that are required for corepressor-coactivator exchange, but whether there is an actual requirement for specific epigenetic landmarks to impose ligand dependency for gene activation remains unknown. Here we report an unexpected and general strategy that is based on the requirement for specific cohorts of inhibitory histone methyltransferases (HMTs) to impose gene-specific gatekeeper functions that prevent unliganded nuclear receptors and other classes of regulated transcription factors from binding to their target gene promoters and causing constitutive gene activation in the absence of stimulating signals. This strategy, based at least in part on an HMT-dependent inhibitory histone code, imposes a requirement for specific histone demethylases, including LSD1, to permit ligand- and signal-dependent activation of regulated gene expression. These events link an inhibitory methylation component of the histone code to a broadly used strategy that circumvents pathological constitutive gene induction by physiologically regulated transcription factors.

Pubmed ID: 17289570 RIS Download

Mesh terms: Cell Line, Tumor | Chromatin Immunoprecipitation | Estradiol | Estrogen Receptor alpha | Gene Expression Regulation | Genome, Human | Histone Code | Histone Demethylases | Histone-Lysine N-Methyltransferase | Histones | Humans | Ligands | Methylation | Oxidoreductases, N-Demethylating | Promoter Regions, Genetic | Transcriptional Activation

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Associated grants

  • Agency: NCI NIH HHS, Id: CA114184
  • Agency: NCI NIH HHS, Id: CA52599
  • Agency: NCI NIH HHS, Id: CA97134
  • Agency: NIDDK NIH HHS, Id: DK063491
  • Agency: NIDDK NIH HHS, Id: DK39949
  • Agency: NHGRI NIH HHS, Id: HG003119
  • Agency: NINDS NIH HHS, Id: NS34934
  • Agency: NCI NIH HHS, Id: R01 CA097134
  • Agency: NIDDK NIH HHS, Id: R01 DK039949
  • Agency: NINDS NIH HHS, Id: R01 NS034934

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