Histone Demethylation Mediated by the Nuclear Amine Oxidase Homolog LSD1

A method of screening for modulators of eukaryotic histone demethylase activity, comprising:

• contacting a eukaryotic histone demethylase protein and a histone peptide in the presence and in the absence of a test substance, wherein the histone peptide is lysine-methylated;
• determining the methylation status of the histone peptide;
• identifying a test substance as an enhancer of eukaryotic histone demethylase activity if less methylated lysine is found in the presence than in the absence of the test substance, and identifying a test substance as an inhibitor of eukaryotic histone demethylase protein activity if more methylated lysine is found in the presence than in the absence of the test substance.

A method for identifying an agent that modulates the interaction between a histone demethylase protein and a CoREST or BHC80 protein, comprising contacting a histone demethylase reagent and a CoREST or BHC80 reagent in the presence of a test agent;

• and (ii) determining the level of interaction between the histone demethylase reagent and the CoREST or BHC80 reagent, wherein a different level of interaction between the histone demethylase reagent and the CoREST or BHC80 reagent in the presence of the test agent relative to the absence of the test agent indicates that the test agent is an agent that modulates the interaction between a histone demethylase protein and a CoREST or BHC80 protein.

A method for identifying an agent that modulates the biological activity of a histone demethylase, comprising:

• (i) contacting a histone demethylase reagent with a CoREST or BHC80 reagent in the presence of a test agent;
• and (ii) determining the biological activity of the histone demethylase reagent, wherein a different activity of the histone demethylase reagent in the presence of the test agent relative to the absence of the test agent indicates that the test agent is an agent that modulates the biological activity of a histone demethylase.

A composition or molecular complex comprising a histone demethylase reagent and a CoREST reagent and/or a BHC80 reagent.

A method for repressing the transcription of a methylated histone activated gene in a cell, comprising contacting the cell with, or administering into the cell, an agent that increases the protein or activity level of a histone demethylase in the cell.

A method for increasing the transcription of a methylated histone activated gene in a cell, comprising contacting the cell with an agent that decreases the protein or activity level of a histone demethylase in the cell.

A method for treating or preventing a disease associated with the abnormal expression of a methylated histone activated gene in a subject, comprising administering to the subject a therapeutically effective amount of an agent that modulates the level of protein or activity of a histone demethylase.