Nature, doi:10.1038/nature12466

The ability to spatially and temporally regulate endogenous gene expression is essential to elucidate gene function. Konermann et al. developed a system called light-inducible transcriptional effectors (LITE), which can either activate or repress gene expression through the application of light. LITE uses two distinct components: a TALE DNA-binding domain recognizing specific promoter elements bound to the light-sensitive cryptochrome 2 (CRY2) protein and the CRY2 partner protein CIB1 fused to a transcriptional effector—in this case, the activator VP64. Application of blue light stimulates the dimerization of CRY2 and CIB1, bringing VP64 to the promoter region, which results in the initiation of transcription. LITE-mediated gene induction was rapid, with increased gene expression detected within 30 min after light stimulation and with a half-life of 3 h. Next, the authors developed an adeno-associated virus vector to introduce LITE constructs into primary cortical neurons activating an array of endogenous neuronal genes through the delivery of light. Interestingly, the authors could also modulate in vivo gene expression specifically in the prefrontal cortex by introducing light through a fibre optic cannula. In addition to controlling gene expression, the authors were able to elicit light-mediated epigenetic changes by using the histone-modifying domains, such as mSin3 (SID4X), to inhibit gene expression through reduction of H3K9 acetylation. Taken together, LITE may be an efficient approach to precisely control mammalian gene expression in specific cell types.