Histone H3 Lysine 4 Demethylation Is a Target of Nonselective Antidepressive Medications

Min Gyu Lee, Christopher Wynder, Dawn M. Schmidt, Dewey G. McCafferty, Ramin Shiekhattar

Research output: Contribution to journalArticle

315 Citations (Scopus)

Abstract

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 μM. 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.

Original languageEnglish (US)
Pages (from-to)563-567
Number of pages5
JournalChemistry and Biology
Volume13
Issue number6
DOIs
StatePublished - Jun 2006
Externally publishedYes

Fingerprint

Tranylcypromine
Histones
Lysine
Monoamine Oxidase
Monoamine Oxidase Inhibitors
Pargyline
Embryonal Carcinoma Stem Cells
Pluripotent Stem Cells
Methylation
Stem cells
Inhibitory Concentration 50
Names
Genes
Cells
Enzymes

Keywords

  • CHEMBIO
  • DNA

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Histone H3 Lysine 4 Demethylation Is a Target of Nonselective Antidepressive Medications. / Lee, Min Gyu; Wynder, Christopher; Schmidt, Dawn M.; McCafferty, Dewey G.; Shiekhattar, Ramin.

In: Chemistry and Biology, Vol. 13, No. 6, 06.2006, p. 563-567.

Research output: Contribution to journalArticle

Lee, Min Gyu ; Wynder, Christopher ; Schmidt, Dawn M. ; McCafferty, Dewey G. ; Shiekhattar, Ramin. / Histone H3 Lysine 4 Demethylation Is a Target of Nonselective Antidepressive Medications. In: Chemistry and Biology. 2006 ; Vol. 13, No. 6. pp. 563-567.
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