A Novel Histone Demethylase And Its 3-D Structure

Tech ID: 06-08

Summary
Histone methylation has been found to be an essential regulator of gene activity.  Both methylation and demethylation may also play important roles in tumorigenesis. Researchers at National Jewish Health and the Harvard Medical School have found a new family of histone demethylases (JMJD2) that remove methyl groups from lysine residues of the histone tails to regulate the transcriptional activity of target genes.  As the JMJD2 family generates different methylated states, they may be important for fine tuning histone methylation and therefore may act as a DNA-damage checkpoint.  Alterations of the expression and/or activities of the JMJD2 family members may also contribute to human diseases such as cancer. Accordingly, inhibition of this demethylating activity could potentially constitute a new anti-neoplastic therapeutic modality.

Potential Applications
Cancer therapy
Cancer diagnostics/personalized medicine

Advantages of Invention
An epigenetic approach to cancer therapy reactivates silenced genes and re-establishes the cancer cell's natural mechanisms to control abnormal growth and therefore does not affect normal cells.

State of Development
· Identified theJMJD2 family as histone dimethylases with specificity for trimethylated H3-K9 and H3-K36.
· Found that decreasing JMJD2A by RNAi triggered apoptosis
· Determined the structure of the catalytic core of the JMJD2A protein

Patent
US and International patent applications pending

Publications
Chen et al. 2007 PNAS June 13, Epub ahead of print
Chen et al. 2006 Cell 125:691-702
Whetstine et al. 2006 Cell 125:1-15

Inventors
Gongyi Zhang, Jianye Zang, Zhongzhou Chen, Yang Shi, Johnathan R. Whetstine

Licensing Status
Available for licensing