Histone demethylation mediated by the nuclear amine oxidase homolog LSD1
AssigneePresident and Fellows of Harvard College
InventorsYang Shi, Yujiang Shi
Life of this patent
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Abstract
LSD1, a homolog of nuclear amine oxidases, functions as a histone demethylase and transcriptional co-repressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription. Lysine demethylation occurs via an oxidation reaction that generates formaldehyde. Importantly, RNAi inhibition of LSD1 causes an increase in H3 lysine 4 methylation and concomitant de-repression of target genes, suggesting that LSD1 represses transcription via histone demethylation. The results thus identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histone methylases and demethylases.
Claims18
A method of screening for modulators of LSD1 or AOF1 activity, comprising:
- contacting a LSD1 or AOF1 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 LSD1 or AOF1 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 LSD1 or AOF1 activity if more methylated lysine is found in the presence than in the absence of the test substance.
A method of screening for modulators of LSD1 activity, comprising:
- contacting a LSD1 protein and a lysine-methlyated histone peptide in the presence and in the absence of a test substance and detecting LSD1 activity.
Dependencies are inferred from the claim text.