Available Technology
Human Histone Deacetylase (HDAC) Class II
Technology:
Nucleic and amino acid sequences of human Class II HDACs
Markets Addressed
Histone deacetylases (HDAC) are a class of enzymes that remove acetyl groups from an epsilon-N-acetyl lysine amino acid on a histone. The first human HDAC was discovered and cloned by the Schreiber laboratory. HDACs are members of an enzyme family conserved in animals, plants, fungi and bacteria. There are three classes of HDACs in humans. Class I enzymes (HDACs 1, 2, 3 and 8) are ubiquitously expressed, predominantly nuclear, and mainly function as transcriptional corepressors. Class II enzyme (HDACs 4, 5, 6, 7, 9 and 10) distribution is more tissue specific, suggesting distinct functions in cellular differentiation and developmental processes.
Histone acetylation plays an important role in the regulation of gene expression. Hyperacetylated chromatin is transcriptionally active, and hypoacetylated chromatin is silent. Also, HDACs interact with a number of non-histone proteins that include transcription factors and co-regulators. HDACs play important roles in a variety of biological pathways, such as those involve in:
• Human diseases: e.g. cancers; chronic myeloid leukemia
• Cellular processes: e.g. cell growth and death; cell cycle
• Environmental information processing: e.g. signal transduction; notch signaling pathway
Innovations and Advantages
Recombinant HDAC proteins are used in biochemical in vitro assays, for raising antibodies against specific HDAC, and as in vitro protein targets in drug discovery approaches towards new HDAC inhibitors.
Non-exclusive research-use license is available for the intellectual properties covering the nucleic and amino acid sequences of human Class II HDACs. Please refer to case HU 1250 for class I HDACs.
Additional Information
Intellectual Property Status: Issued U.S. patent nos.: 7,250,504; 8,076,116
Selected References:
HDAC1:
Taunton J, Hassig CA, Schreiber SL. 1996. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science. 272(5260):408-11.
HDAC2:
Yang, W.-M., Inouye, C., Zeng, Y., Bearss, D., and Seto, E. 1996. Proc. Natl. Acad. Sci. U. S. A. 93(23):12845-50.
HDAC3:
Yang WM, Yao YL, Sun JM, Davie JR, Seto E. 1997. Isolation and characterization of cDNAs corresponding to an additional member of the human histone deacetylase gene family. J Biol Chem. 272(44):28001-7.
HDAC 4-6:
Grozinger CM, Hassig CA, Schreiber SL. 1999. Three proteins define a class of human histone deacetylases related to yeast Hda1p. Proc Natl Acad Sci U S A. 96(9):4868-73.
HDAC7:
Kao, H.-Y., Downes, M., Ordentlich, P., and Evans, R. M. 2000. Isolation of a novel histone deacetylase reveals that class I and class II deacetylases promote SMRT-mediated repression. Gene Dev. 14, 55-66
HDAC8:
Hu E, Chen Z, Fredrickson T, Zhu Y, Kirkpatrick R, Zhang GF, Johanson K, Sung CM, Liu R, Winkler J. 2000. Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor. J Biol Chem. 275(20):15254-64.
HDAC 9:
Zhou X, Marks PA, Rifkind RA, Richon VM. 2001. Cloning and characterization of a histone deacetylase, HDAC9. Proc Natl Acad Sci U S A. 98(19):10572-7.
HDAC 10:
Tong JJ, Liu J, Bertos NR, Yang X. 2002. Identification of HDAC10, a novel class II human histone deacetylase containing a leucine-rich domain. Nucleic Acids Res. 30(5):1114-23.
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Inventor(s):
Grozinger, Christina M.
Hassig, Christian A.
Schreiber, Stuart L.
Categories:
For further information, please contact:
Laura Brass, Director of Business Development
(617) 495-3067
Reference Harvard Case #1675