[ExI] Optogenetics for transcription and epigenetics

[Anders Sandberg]

This is pretty nifty: optical control of gene expression and epigenetics 
in nerve cells. Like optogenetics, but allowing primed cells to be 
transformed by laser.

http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html
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 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^1 
> <http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref1>, 
> 2 
> <http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref2>, 
> 3 
> <http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref3>, 
> 4 
> <http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref4>, 
> 5 
> <http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref5>, 
> 6 
> <http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref6>, 
> 7 
> <http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref7>, 
> 8 
> <http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref8>, 
> 9 
> <http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref9>, 
> 10 
> <http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref10>, 
> 11 
> <http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref11> 
> . 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^12 
> <http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref12>, 
> 13 
> <http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref13>, 
> 14 
> <http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref14> 
> 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^6 
> <http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref6>, 
> 15 
> <http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature12466.html#ref15> 
> . 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.

-- 
Anders Sandberg,
Future of Humanity Institute
Oxford Martin School
Faculty of Philosophy
Oxford University

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