title: Light-controlled modulation of gene expression by chemical optoepigenetic probes.
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.
authors.affiliation: Chemical Neurobiology Laboratory, Massachusetts General Hospital, Boston, Massachusetts, USA.|Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Surya A
authors.initials: SA
authors.lastname: Reis
authors.affiliation: Chemical Neurobiology Laboratory, Massachusetts General Hospital, Boston, Massachusetts, USA.|Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA.|Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Balaram
authors.initials: B
authors.lastname: Ghosh
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: J Adam
authors.initials: JA
authors.lastname: Hendricks
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: D Miklos
authors.initials: DM
authors.lastname: Szantai-Kis
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Törk
authors.affiliation: Center for Cancer Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Ross
authors.affiliation: Genometry Inc., Cambridge, Massachusetts, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Lamb
authors.affiliation: Genometry Inc., Cambridge, Massachusetts, USA.
authors.forename: Willis
authors.initials: W
authors.lastname: Read-Button
authors.affiliation: Genometry Inc., Cambridge, Massachusetts, USA.
authors.forename: Baixue
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Department of Electrical &Computer Engineering, University of Massachusetts, Amherst, Massachusetts, USA.|Center for Personalized Health Monitoring, University of Massachusetts, Amherst, Massachusetts, USA.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Electrical &Computer Engineering, University of Massachusetts, Amherst, Massachusetts, USA.|Center for Personalized Health Monitoring, University of Massachusetts, Amherst, Massachusetts, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Salthouse
authors.affiliation: Chemical Neurobiology Laboratory, Massachusetts General Hospital, Boston, Massachusetts, USA.|Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA.|Broad Institute of Harvard &Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Haggarty
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.|Broad Institute of Harvard &Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Mazitschek
mesh_terms: D001391:Azo Compounds / Q000737:chemistry; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D008027:Light; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D062308:Optogenetics / Q000379:methods*
chemical_list: D001391:Azo Compounds; C009850:azobenzene