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Transcript
Nidhi Sabharwal, Ph.D.
Assistant Director
Office of Technology Transfer
(212) 327-7092
[email protected]
Binary Switches in Gene Expression: The Histone Code
RU 665
Technology Summary
The human body contains multiple organs and diverse cell types. Although every gene in the
human genome exists within every cell, only a small percentage of genes are activated in any given cell
type. These different gene expression profiles are formulated during early development in a multicellular
organism, when cell division, cell differentiation, tissue and organ formation rapidly occur. Moreover,
this gene expression potential can be “memorized” and inherited after mitosis and even meiosis. To
regulate this genetic information, nature has evolved a sophisticated system that controls access to
specific genes resulting in “epigenetic” information, i.e. a form of inherited states of gene regulation that
lies outside of the DNA itself. . This system relies on packaging DNA into a DNA-histone complex
called chromatin, which is the physiological substrate of all cellular processes involving the DNA. The
dynamic change of the three-dimensional architecture of chromatin makes certain genes more readily
accessible to transcription factors and other machineries that must engage the genetic template.
The central building blocks of the chromatin polymer are a family of proteins named histones.
Dynamic processes that covalently modify histones play critical roles in regulating gene expression.
Misregulation of the “on” and “off” dynamics of histone modifications can lead to diseases such as
cancer. Histone acetylation and methylation prevent DNA from coiling tightly, allowing associated genes
to be expressed. The opposite processes, deacetylation and demethylation, allow the DNA to coil tightly
thereby preventing gene expression.
In sum, chromatin is the physiological template of our genome. As such, the epigenetic
information carried by the chromatin polymer impacts on most of the chromatin-templated processes with
far-reaching consequences for cell fate decisions and for normal and pathological development. Our
scientists have proposed that there is an epigenetic indexing system for our genome, a “histone or
epigenetic code,” that works as a fundamental regulatory mechanism in addition to the DNA and the
genetic information itself. Distinct covalent histone modifications, acting alone, sequentially or in
combination, form a “histone code” that is then read by effector proteins to bring about distinct
downstream events. They are currently focusing on identifying what “writes” and what “reads” the
histone code.
Area of Application
 Modulation of a chromatin-binding protein or protein complex as a way to treat disease.
Stage of Development
 Discovery
Lead Inventor
 Dr. C. David Allis
Patent Information
 U.S. Patent 8,404, 458 (issued March 26, 2013)
References
 Fischle, et al. 2003. Nature, 425:475-479.
The Rockefeller University Office of Technology Transfer
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