We engineered a photoactivatable system for rapidly and reversibly exporting proteins from the nucleus by embedding a nuclear export signal in the LOV2 domain from phototropin 1. Fusing the chromatin modifier Bre1 to the photoswitch, we achieved light-dependent control of histone H2B monoubiquitylation in yeast, revealing fast turnover of the ubiquitin mark. Moreover, this inducible system allowed us to dynamically monitor the status of epigenetic modifications dependent on H2B ubiquitylation.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Molecular Brain Open Access 04 January 2022
npj Systems Biology and Applications Open Access 11 March 2021
Nature Communications Open Access 13 August 2020
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Tischer, D. & Weiner, O.D. Nat. Rev. Mol. Cell Biol. 15, 551–558 (2014).
Yang, X., Jost, A.P.-T., Weiner, O.D. & Tang, C. Mol. Biol. Cell 24, 2419–2430 (2013).
Gautier, A. et al. J. Am. Chem. Soc. 132, 4086–4088 (2010).
Yumerefendi, H. et al. PLoS One 10, e0128443 (2015).
Niopek, D. et al. Nat. Comm. 5, 4404 (2014).
Harper, S.M., Neil, L.C. & Gardner, K.H. Science 301, 1541–1544 (2003).
Zayner, J.P., Antoniou, C. & Sosnick, T.R. J. Mol. Biol. 419, 61–74 (2012).
Hutten, S. & Kehlenbach, R.H. Trends Cell Biol. 17, 193–201 (2007).
Güttler, T. et al. Nat. Struct. Mol. Biol. 17, 1367–1376 (2010).
Hodel, M.R., Corbett, A.H. & Hodel, A.E. J. Biol. Chem. 276, 1317–1325 (2001).
Guntas, G. et al. Proc. Natl. Acad. Sci. USA 112, 112–117 (2015).
Hodel, A.E. et al. J. Biol. Chem. 281, 23545–23556 (2006).
Xiao, T. et al. Mol. Cell. Biol. 25, 637–651 (2005).
Fuchs, G., Hollander, D., Voichek, Y., Ast, G. & Oren, M. Genome Res. 24, 1572–1583 (2014).
Henry, K.W. et al. Genes Dev. 17, 2648–2663 (2003).
Kosugi, S., Hasebe, M., Tomita, M. & Yanagawa, H. Proc. Natl. Acad. Sci. USA 106, 10171–10176 (2009).
Sun, Z.-W. & Allis, C.D. Nature 418, 104–108 (2002).
Briggs, S.D. et al. Nature 418, 498 (2002).
Huang, F. et al. J. Biol. Chem. http://dx.doi.org/10.1074/jbc.M115.693085 (2015).
Katan-Khaykovich, Y. & Struhl, K. EMBO J. 24, 2138–2149 (2005).
Cai, L., Makhov, A.M., Schafer, D.A. & Bear, J.E. Cell 134, 828–842 (2008).
Hallett, R.A., Zimmerman, S.P., Yumerefendi, H., Bear, J.E. & Kuhlman, B. ACS Synth. Biol. 5, 53–64 (2016).
Gietz, R.D. & Schiestl, R.H. Nat. Protoc. 2, 35–37 (2007).
We would like to thank D. Dickinson for help with C. elegans injections, H. Meriesh for providing a plasmid containing BRE1, and R. Dronamraju and Z.-W. Sun for helpful discussions. Funding: J.E.B. (NIH GM111557), B.K., K.H., B.S. (NIH DA036877), K.H. (GM102924).
The authors declare no competing financial interests.
Supplementary Results, Supplementary Figures 1–13, Supplementary Tables 1–4 and Supplementary Note. (PDF 19788 kb)
The appearance and disappearance of a square indicate the area and the time of blue light activation. Scale bar is 50 μm. (MOV 6347 kb)
The appearance and disappearance of a square indicate the area and the time of blue light activation. Scale bar is 50 μm. (MOV 8240 kb)
The appearance and disappearance of a square indicate the area and the time of blue light activation. Scale bar is 100 μm. (MOV 9768 kb)
The appearance and disappearance of a square indicate the area and the time of blue light activation. Scale bar is 50 μm. (MOV 22837 kb)
Activation is performed on the entire field of view and is indicated with words at the upper left corner. Scale bar is 10 μm. (MOV 14408 kb)
Two cycles of blue light activation and reversion of LINXa3-nano (red color) and iLID-Mito (green color) in mouse fibroblast cells (IA32)
The appearance and disappearance of a square indicate the area and the time of blue light activation. Scale bar is 50 μm. (MOV 28412 kb)
Activation and reversion of LINXa4-Bre1 (green color) in an H2B-mCherry (labels the nucleus in red) yeast strain (Supplementary Table 3)
The appearance and disappearance of a square indicate the area and the time of blue light activation. Scale bar is 10 μm. (MOV 9449 kb)
About this article
Cite this article
Yumerefendi, H., Lerner, A., Zimmerman, S. et al. Light-induced nuclear export reveals rapid dynamics of epigenetic modifications. Nat Chem Biol 12, 399–401 (2016). https://doi.org/10.1038/nchembio.2068
This article is cited by
Molecular Brain (2022)
npj Systems Biology and Applications (2021)
Nature Communications (2020)
Near-infrared light–controlled systems for gene transcription regulation, protein targeting and spectral multiplexing
Nature Protocols (2018)
Nature Chemical Biology (2017)