2. Academic Validation
  3. Light-controlled modulation of gene expression by chemical optoepigenetic probes

Light-controlled modulation of gene expression by chemical optoepigenetic probes

  • Nat Chem Biol. 2016 May;12(5):317-23. doi: 10.1038/nchembio.2042.
Surya A Reis 1 2 3,  Balaram Ghosh 1 2 3 4,  J Adam Hendricks 4,  D Miklos Szantai-Kis 4,  Lisa Törk 4,  Kenneth N Ross 5,  Justin Lamb 6,  Willis Read-Button 6,  Baixue Zheng 6,  Hongtao Wang 7 8,  Christopher Salthouse 7 8,  Stephen J Haggarty 1 2 3 9,  Ralph Mazitschek 4 9
Affiliations

Affiliations

  • 1 Chemical Neurobiology Laboratory, Massachusetts General Hospital, Boston, Massachusetts, USA.
  • 2 Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
  • 3 Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA.
  • 4 Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 5 Center for Cancer Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
  • 6 Genometry Inc., Cambridge, Massachusetts, USA.
  • 7 Department of Electrical &Computer Engineering, University of Massachusetts, Amherst, Massachusetts, USA.
  • 8 Center for Personalized Health Monitoring, University of Massachusetts, Amherst, Massachusetts, USA.
  • 9 Broad Institute of Harvard &Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
PMID: 26974814 DOI: 10.1038/nchembio.2042
Abstract

Epigenetic gene regulation is a dynamic process orchestrated by chromatin-modifying enzymes. Many of these master regulators exert their function through covalent modification of DNA and histone proteins. Aberrant epigenetic processes have been implicated in the pathophysiology of multiple human diseases. Small-molecule inhibitors have been essential to advancing our understanding of the underlying molecular mechanisms of epigenetic processes. However, the resolution offered by small molecules is often insufficient to manipulate epigenetic processes with high spatiotemporal control. Here we present a generalizable approach, referred to as 'chemo-optical modulation of epigenetically regulated transcription' (COMET), enabling high-resolution, optical control of epigenetic mechanisms based on photochromic inhibitors of human histone deacetylases using visible LIGHT. COMET probes may be translated into new therapeutic strategies for diseases where conditional and selective epigenome modulation is required.

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