R. Keith Slotkin
Associate Professor/Associate Member and Principal Investigator
Division of Biological Sciences/Donald Danforth Plant Science Center
E-mail: kslotkin at danforthcenter dot org
Office phone: 314-587-1425
Transposable elements are fragments of DNA that can duplicate or move from one location to another. Their ability to replicate has resulted in transposable elements occupying vast amounts of most eukaryotic genomes, including nearly half of the human genome. Although often overlooked or dismissed as “junk DNA”, transposable elements have played an important role in the structure and evolution of the eukaryotic genome.
When transposable elements are active, they cause DNA damage and new mutations by inserting into essential protein-coding genes or by promoting rearrangements and genome instability. To suppress the mutagenic potential of transposable elements, over a billion years ago eukaryotes evolved a genome-wide surveillance system to target transposable elements for inactivation. This process of selective inactivation takes advantage of the transposable element’s propensity to generate double-stranded RNA, which is the trigger for small RNA-based silencing mechanisms. These silencing mechanisms result in either post-transcriptional silencing or chromatin modifications. One such heritable chromatin modification is DNA methylation, which can be propagated from cell to cell (through mitosis) or from parent to progeny (through meiosis and fertilization). This heritable repression of gene expression is referred to as epigenetic regulation, and is not the result of changes in the primary DNA sequence (ATGCs). Epigenetic changes are distinct from genetic changes because they are readily reversible, making them exceptional targets of short-term or generation-to-generation environmental modulation.
My laboratory uses Arabidopsis thaliana (thale cress), a reference flowering plant, as a model to investigate basic biological questions exploring how eukaryotic cells repress transposable elements over the development of a single generation, as well as across evolutionary time. Plants offer a unique opportunity to study transposable elements. Unlike animals, plants lack a germline that is set-aside early in embryonic development, meaning that epigenetic changes that occur during plant development are more likely to be transmitted to the next generation. Furthermore, mutations in the genes responsible for epigenetically suppressing transposable elements in plants are viable, while the corresponding mutations that act similarly to silence transposable elements in mammals are embryonic lethal.
Projects in the laboratory focus on the following:
- How the cell recognizes which regions of the genome are genes and should be expressed, and which are transposable elements and should be selectively silenced
- How epigenetic information targeting transposable elements for silencing is propagated from generation to generation, protecting each generation from new mutations
- Determining how active transposable elements are initially triggered for silencing and how epigenetic modifications are first targeted.
- Understanding how the recruitment of epigenetic control to transposable elements has been co-opted over evolutionary time to produce novel and interesting examples of gene regulation.
To view my plea to the biology community not to overlook transposable elements, see:
Slotkin, R. K. (2018) The case for not masking away repetitive DNA. Mobile DNA, 9(1), p. 475.
For more information on the epigenetic regulation of transposable elements, see:
Sigman, M. J. and Slotkin, R. K. (2016) The first rule of plant transposable element silencing: location, location, location. The Plant Cell, 28(2), pp. 304–313.
For more information on the mechanisms of small RNA-directed DNA Methylation, see:
Cuerda-Gil, D. and Slotkin, R. K. (2016) Non-canonical RNA-directed DNA methylation. Nature Plants, 2(11), p. 16163.
- Nominated for a Distinguished Undergraduate Research Mentor Award, Undergraduate Research Office, The Ohio State University (2014 )
- Kavli Frontiers of Science Fellow, US National Academy of Sciences (2013)
- Early Career Award from the American Society of Plant Biologists (ASPB) (2010 )
2018 G. Martinez, P. Wolff, Z. Wang, J. Moreno-Romero, J. Santos-González, L.L. Conze, C.
DeFraia, R.K. Slotkin and C. Köhler. Paternal easiRNAs regulate parental genome dosage in Arabidopsis. Nature Genetics v50:193-198.
2017 J. Daron and R.K. Slotkin. EpiTEome: Simultaneous detection of transposable
element insertion sites and their DNA methylation levels. Genome Biology v18:7704. https://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1232-0
2017 D. Fultz and R.K. Slotkin. Exogenous Transposable Elements Circumvent Identity-Based Silencing Permitting the Dissection of Expression Dependent Silencing. The Plant Cell v29:360-376. http://www.plantcell.org/content/early/2017/02/13/tpc.16.00718
2017 G. Martinez, S. Choudury and R.K. Slotkin. tRNA-derived small RNAs target transposable element transcripts. Nucleic Acids Research v45:5142-52.
2016 K. Panda, L. Ji, D.A. Neumann, J. Daron, R.J. Schmitz and R.K. Slotkin. Full-length autonomous transposable elements are preferentially targeted by expression-dependent forms of RNA-directed DNA methylation. Genome Biology v17: 170.
2016 G. Martinez, K. Panda, C. Köhler and R.K. Slotkin. Silencing in sperm cells is directed by RNA movement from the surrounding nurse cell. Nature Plants v2: 16030
News & Views in Nature Plants:
In Brief Research Highlight in Nature Reviews Molecular Cell Biology:
2015 A.D. McCue, K. Panda, S. Nuthikattu, S.G. Choudury, E.N. Thomas and R.K. Slotkin. ARGONAUTE6 bridges transposable element mRNA-derived siRNAs to the establishment of DNA methylation. EMBO Journal v34: 20-35.
Research Highlight in EMBO Journal: http://emboj.embopress.org/content/early/2015/01/28/embj.201590971
Non-Coding RNA Journal Club Highlights on Recent Papers:
2013 S. Nuthikattu, A.D. McCue, K. Panda, D. Fultz, C. DeFraia, E.N. Thomas and R.K. Slotkin. The Initiation of Epigenetic Silencing of Active Transposable Elements is Triggered by RDR6 and 21-22 Nucleotide Small Interfering RNAs. Plant Physiology v162: 116-131.
Faculty of 1000 selected publication: http://f1000.com/prime/717996637
2013 A.D. McCue, S. Nuthikattu, and R.K. Slotkin. Genome-wide Identification of Genes Regulated in trans by Transposable Element Small Interfering RNAs. RNA Biology v10: 1379-1395.
2012 A.D. McCue, S. Nuthikattu, S.H. Reeder and R.K. Slotkin. Gene Expression
and Stress Response Mediated by the Epigenetic Regulation of Transposable Element Small RNA. PLoS Genetics v8: e1002474
2012 F. Borges, R. Gardner, T. Lopes, J.P. Calarco, L.C. Boavida, R.K. Slotkin, R.A.
Martienssen, and J.D. Becker. FACS-based Purification of Arabidopsis Microspores, Sperm Cells and Vegetative Nuclei. Plant Methods v8: 44.
2011 F. Borges, P.A. Pereira, R.K. Slotkin, R.A. Martienssen and J.D. Becker. MicroRNA activity in the Arabidopsis male germline. Journal of Experimental Botany v62: 1611-1620.
2011 N. Jiang, A.A. Ferguson, R.K. Slotkin and D. Lisch. Pack-MULE
transposable elements induce directional modification of genes through biased insertion and DNA acquisition. Proceedings of the National Academy of Sciences USA v108: 1537-1542.
2010 V. Olmedo-Monfil, N. Duran-Figueroa, M. Arteaga-Vazquez, E. Demesa-Arevalo, D. Autran, D. Grimanelli, R.K. Slotkin, R.A. Martienssen, J.-P. Vielle-Calzada. Control of female gamete formation by a small RNA pathway in Arabidopsis. Nature v464: 628-632.
Faculty of 1000 selected publication: http://f1000.com/prime/2527958
2009 R.K. Slotkin, M. Vaughn, M. Tanurdzic, F. Borges, J.D. Becker, J. Feijo and R.A.
Martienssen. Epigenetic reprogramming and small RNA silencing of transposable elements in pollen. Cell v136: 461-472.
Research Highlight in Nature Reviews Genetics: http://www.nature.com/nrg/journal/v10/n4/full/nrg2565.html
Perspective in Science:
Faculty of 1000 selected publication: http://f1000.com/prime/1157170
2009 K. Hanada, V. Vallejo, K. Nobuta, R.K. Slotkin, D. Lisch, B. Meyers, S.-H. Shiu and N.Jiang. The Functional Role of Pack-MULEs in Rice Inferred from Purifying Selection and Expression Profile. The Plant Cell v21: 25-38.
2008 M. Tanurdzic, M. Vaughn, H. Jiang, T.-J. Lee, R.K. Slotkin, B. Sosinski, W.F.
Thompson, R.F. Doerge and R.A. Martienssen. Epigenomic Consequences of Immortalized Plant Cell Suspension Culture. PLoS Biology v6: e302
Faculty of 1000 selected publication: http://f1000.com/prime/1147860
2008 E. Gruntman*, Y. Qi*, R.K. Slotkin*, T. Roeder, R.A. Martienssen and R.
Sachidanandam. Kismeth: Analyzer of Plant Methylation States Through Bisulfite Sequencing. BMC Bioinformatics v9: e371
*These authors contributed equally to this manuscript
2005 R.K. Slotkin, M. Freeling and D. Lisch. Heritable transposon silencing initiated by a naturally occurring transposon inverted duplication. Nature Genetics v37:
2003 R.K. Slotkin, M. Freeling and D. Lisch. Mu killer causes the heritable inactivation of the Mutator family of transposable elements in Zea mays. Genetics v165: 781-797