Optical control of mammalian endogenous transcription and epigenetic states
The dynamic nature of gene expression enables cellular programming, homeostasis and environmental adaptation in living systems. Dissection of causal gene functions in cellular and organismal processes therefore necessitates approaches that enable spatially and temporally precise modulation of gene e...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2016
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| Online Access: | http://hdl.handle.net/1721.1/102696 https://orcid.org/0000-0003-2782-2509 https://orcid.org/0000-0001-7915-1685 https://orcid.org/0000-0002-2639-9879 |
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| author | Konermann, Silvana M. Brigham, Mark D. Trevino, Alexandro E. Hsu, Patrick Heidenreich, Matthias Cong, Le Platt, Randall Jeffrey Scott, David Arthur Church, George M. Zhang, Feng |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Konermann, Silvana M. Brigham, Mark D. Trevino, Alexandro E. Hsu, Patrick Heidenreich, Matthias Cong, Le Platt, Randall Jeffrey Scott, David Arthur Church, George M. Zhang, Feng |
| author_sort | Konermann, Silvana M. |
| collection | MIT |
| description | The dynamic nature of gene expression enables cellular programming, homeostasis and environmental adaptation in living systems. Dissection of causal gene functions in cellular and organismal processes therefore necessitates approaches that enable spatially and temporally precise modulation of gene expression. Recently, a variety of microbial and plant-derived light-sensitive proteins have been engineered as optogenetic actuators, enabling high-precision spatiotemporal control of many cellular functions. However, versatile and robust technologies that enable optical modulation of transcription in the mammalian endogenous genome remain elusive. Here we describe the development of light-inducible transcriptional effectors (LITEs), an optogenetic two-hybrid system integrating the customizable TALE DNA-binding domain with the light-sensitive cryptochrome 2 protein and its interacting partner CIB1 from Arabidopsis thaliana. LITEs do not require additional exogenous chemical cofactors, are easily customized to target many endogenous genomic loci, and can be activated within minutes with reversibility. LITEs can be packaged into viral vectors and genetically targeted to probe specific cell populations. We have applied this system in primary mouse neurons, as well as in the brain of freely behaving mice in vivo to mediate reversible modulation of mammalian endogenous gene expression as well as targeted epigenetic chromatin modifications. The LITE system establishes a novel mode of optogenetic control of endogenous cellular processes and enables direct testing of the causal roles of genetic and epigenetic regulation in normal biological processes and disease states. |
| first_indexed | 2024-09-23T16:37:22Z |
| format | Article |
| id | mit-1721.1/102696 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:37:22Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1026962022-09-29T20:24:57Z Optical control of mammalian endogenous transcription and epigenetic states Konermann, Silvana M. Brigham, Mark D. Trevino, Alexandro E. Hsu, Patrick Heidenreich, Matthias Cong, Le Platt, Randall Jeffrey Scott, David Arthur Church, George M. Zhang, Feng Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences McGovern Institute for Brain Research at MIT Konermann, Silvana M. Brigham, Mark D. Trevino, Alexandro E. Hsu, Patrick Heidenreich, Matthias Cong, Le Platt, Randall Jeffrey Scott, David Arthur Zhang, Feng The dynamic nature of gene expression enables cellular programming, homeostasis and environmental adaptation in living systems. Dissection of causal gene functions in cellular and organismal processes therefore necessitates approaches that enable spatially and temporally precise modulation of gene expression. Recently, a variety of microbial and plant-derived light-sensitive proteins have been engineered as optogenetic actuators, enabling high-precision spatiotemporal control of many cellular functions. However, versatile and robust technologies that enable optical modulation of transcription in the mammalian endogenous genome remain elusive. Here we describe the development of light-inducible transcriptional effectors (LITEs), an optogenetic two-hybrid system integrating the customizable TALE DNA-binding domain with the light-sensitive cryptochrome 2 protein and its interacting partner CIB1 from Arabidopsis thaliana. LITEs do not require additional exogenous chemical cofactors, are easily customized to target many endogenous genomic loci, and can be activated within minutes with reversibility. LITEs can be packaged into viral vectors and genetically targeted to probe specific cell populations. We have applied this system in primary mouse neurons, as well as in the brain of freely behaving mice in vivo to mediate reversible modulation of mammalian endogenous gene expression as well as targeted epigenetic chromatin modifications. The LITE system establishes a novel mode of optogenetic control of endogenous cellular processes and enables direct testing of the causal roles of genetic and epigenetic regulation in normal biological processes and disease states. National Institutes of Health (U.S.) (NIH NHGRI CEGS grant (P50-HG005550)) National Institutes of Health (U.S.) (NIH Transformative R01 award (R01-NS073124)) National Institutes of Health (U.S.) (NIH Director’s Pioneer Award (DP1-MH100706)) 2016-05-26T20:36:43Z 2016-05-26T20:36:43Z 2013-07 2013-02 Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/102696 Konermann, Silvana, Mark D. Brigham, Alexandro Trevino, Patrick D. Hsu, Matthias Heidenreich, Le Cong, Randall J. Platt, David A. Scott, George M. Church, and Feng Zhang. “Optical Control of Mammalian Endogenous Transcription and Epigenetic States.” Nature (July 23, 2013). https://orcid.org/0000-0003-2782-2509 https://orcid.org/0000-0001-7915-1685 https://orcid.org/0000-0002-2639-9879 en_US http://dx.doi.org/10.1038/nature12466 Nature Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC |
| spellingShingle | Konermann, Silvana M. Brigham, Mark D. Trevino, Alexandro E. Hsu, Patrick Heidenreich, Matthias Cong, Le Platt, Randall Jeffrey Scott, David Arthur Church, George M. Zhang, Feng Optical control of mammalian endogenous transcription and epigenetic states |
| title | Optical control of mammalian endogenous transcription and epigenetic states |
| title_full | Optical control of mammalian endogenous transcription and epigenetic states |
| title_fullStr | Optical control of mammalian endogenous transcription and epigenetic states |
| title_full_unstemmed | Optical control of mammalian endogenous transcription and epigenetic states |
| title_short | Optical control of mammalian endogenous transcription and epigenetic states |
| title_sort | optical control of mammalian endogenous transcription and epigenetic states |
| url | http://hdl.handle.net/1721.1/102696 https://orcid.org/0000-0003-2782-2509 https://orcid.org/0000-0001-7915-1685 https://orcid.org/0000-0002-2639-9879 |
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