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LSD1-mediated demethylation of histone H3 lysine 4 triggers Myc-induced transcription.

Authors: Amente, S  Bertoni, A  Morano, A  Lania, L  Avvedimento, EV  Majello, B 
Citation: Amente S, etal., Oncogene. 2010 Jun 24;29(25):3691-702. doi: 10.1038/onc.2010.120. Epub 2010 Apr 26.
Pubmed: (View Article at PubMed) PMID:20418916
DOI: Full-text: DOI:10.1038/onc.2010.120

Myc is a transcription factor that significantly contributes to cancer progression by modulating the expression of important genes through binding to a DNA sequence, CACGTG, called E-box. We find that on Myc binding to chromatin, the lysine-demethylating enzyme, LSD1, triggers a transient demethylation of lysine 4 in the histone H3. In addition, we demonstrate that Myc binds and recruits LSD1 to the E-box chromatin and the formation of this complex is stimulated by cAMP-PKA. Demethylation by LSD1 produces H(2)O(2), which locally oxidizes guanine and induces the recruitment of 8-oxoguanine-DNA glycosylase (OGG1) and of the nuclease Ape1 on the E-box chromatin. Inhibition of oxidation or silencing of LSD1, OGG1 or Ape1 significantly reduce transcription and inhibit mRNA accumulation of Myc-target genes. Collectively, these data highlight the role of transient LSD1-mediated demethylation of H3K4 leading to local DNA oxidation as driving force in the assembly of the Myc-induced transcription initiation complex.

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CRRD Object Information
CRRD ID: 9588315
Created: 2014-10-28
Species: All species
Last Modified: 2014-10-28
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.