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Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications.

Publication ,  Journal Article
Lee, MG; Wynder, C; Schmidt, DM; McCafferty, DG; Shiekhattar, R
Published in: Chemistry & biology
June 2006

Demethylation of histone H3 lysine 4 is carried out by BHC110/LSD1, an enzyme with close homology to monoamine oxidases (MAO). Monoamine oxidase A or B are frequent targets of selective and nonselective small molecular inhibitors used for treatment of depression. Here we show that in contrast to selective monoamine oxidase inhibitors such as pargyline, nonselective monoamine oxidase inhibitors potently inhibit nucleosomal demethylation of histone H3 lysine 4. Tranylcypromine (brand name Parnate) displayed the best inhibitory activity with an IC50 of less than 2 microM. Treatment of P19 embryonal carcinoma cells with tranylcypromine resulted in global increase in H3K4 methylation as well as transcriptional derepression of two BHC110 target genes, Egr1 and the pluripotent stem cell marker Oct4. These results attest to the effectiveness of tranylcypromine as a small molecular inhibitor of histone demethylation.

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Published In

Chemistry & biology

DOI

EISSN

1879-1301

ISSN

1074-5521

Publication Date

June 2006

Volume

13

Issue

6

Start / End Page

563 / 567

Related Subject Headings

  • Tranylcypromine
  • Organic Chemistry
  • Nucleosomes
  • Monoamine Oxidase Inhibitors
  • Monoamine Oxidase
  • Molecular Structure
  • Methylation
  • Lysine
  • Humans
  • Histones
 

Citation

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Lee, M. G., Wynder, C., Schmidt, D. M., McCafferty, D. G., & Shiekhattar, R. (2006). Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications. Chemistry & Biology, 13(6), 563–567. https://doi.org/10.1016/j.chembiol.2006.05.004
Lee, Min Gyu, Christopher Wynder, Dawn M. Schmidt, Dewey G. McCafferty, and Ramin Shiekhattar. “Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications.Chemistry & Biology 13, no. 6 (June 2006): 563–67. https://doi.org/10.1016/j.chembiol.2006.05.004.
Lee MG, Wynder C, Schmidt DM, McCafferty DG, Shiekhattar R. Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications. Chemistry & biology. 2006 Jun;13(6):563–7.
Lee, Min Gyu, et al. “Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications.Chemistry & Biology, vol. 13, no. 6, June 2006, pp. 563–67. Epmc, doi:10.1016/j.chembiol.2006.05.004.
Lee MG, Wynder C, Schmidt DM, McCafferty DG, Shiekhattar R. Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications. Chemistry & biology. 2006 Jun;13(6):563–567.

Published In

Chemistry & biology

DOI

EISSN

1879-1301

ISSN

1074-5521

Publication Date

June 2006

Volume

13

Issue

6

Start / End Page

563 / 567

Related Subject Headings

  • Tranylcypromine
  • Organic Chemistry
  • Nucleosomes
  • Monoamine Oxidase Inhibitors
  • Monoamine Oxidase
  • Molecular Structure
  • Methylation
  • Lysine
  • Humans
  • Histones