
R. Keith Slotkin
Associate Professor
Danforth Center
975 N. Warson Rd
St. Louis, MO
63132
Areas of Expertise
- Epigenetics
- Transposable Elements
- Small RNAs
Education
- PhD – The University of California Berkeley (2000-2005)
- Post-Doctoral Research – Cold Spring Harbor Laboratory (2005-2009)
- Bachelor of Science - The University of Arizona (1996-2000)
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.
For more information on the epigenetic regulation of transposable elements, see Sigman and Slotkin, 2016, The Plant Cell.
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:
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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
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How epigenetic information targeting transposable elements for silencing is propagated from generation to generation, protecting each generation from new mutations
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How active transposable elements are initially triggered for silencing and how epigenetic modifications are first targeted.
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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.
Current Lab Members:
- Josquin Daron (Postdoc)
- Kaushik Panda (Graduate Student)
- Dalen Fultz (Graduate Student)
- Sarah Choudury (Graduate Student)
- Meredith Sigman (Graduate Student)
- Diego Cuerda-Gil (graduate student)
- Alissa Cullen (Undergraduate Research Assistant)
Lab Alumni:
- Germán Martinez-Arias (Postdoc) is currently a Senior Researcher in the laboratory of Claudia Köhler at the Swedish University of Agricultural Sciences
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Chris DeFraia (Postdoc) is currently an Assistant Professor at Ferris State University
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Andrea McCue (Graduate Student) is currently a Postdoc at the NIH in the lab of Shiv Grewal
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Saivageethi Nuthikattu (Graduate Student) is currently a Postdoc at the University of California Davis in the lab of Amparo Villablanca
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Erica Thomas (Undergraduate Student) is currently in a PhD program at Washington University in St. Louis in the lab of Hani Zaher
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Jennifer Bosse (Undergraduate Student) is currently in the MCDB Graduate program at The Ohio State University in the lab of Heithem El-Hodiri
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Jeff Kovach (Undergraduate Student) is currently studying plant biology in a PhD program at Michigan State University
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Eric Roose (Undergraduate Student) is currently completing a post-bac pre-med program at the University of Toledo
Publications:
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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 2, 16030.
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2016 M.J. Sigman and R.K. Slotkin. The First Rule of Plant Transposable Element Silencing: Location, Location, Location. The Plant Cell 28, 304–313.
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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 17, 100.
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2015 D. Fultz, S.G. Choudury and R. Keith Slotkin. Silencing of Active Transposable Elements in Plants. Current Opinion in Plant Biology v27:67-76.
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2015 A.D. McCue, K. Panda, S. Nuthikattu, S.G. Choudury, E.N. Thomas and R. Keith Slotkin. ARGONAUTE 6 bridges transposable element mRNA-derived siRNAs to the establishment of DNA methylation. EMBO Journal v34: 20-35.
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2013 S. Nuthikattu, A.D. McCue, K. Panda, D. Fultz, C. DeFraia, E.N. Thomas and R. Keith 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.
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2013 A.D. McCue, S. Nuthikattu, and R. Keith Slotkin. Genome-wide Identification of Genes Regulated in trans by Transposable Element Small Interfering RNAs. RNA Biology v10: 1379-1395.
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2013 Patrice Dunoyer, Charles Melnyk, Attila Molnar, and R. Keith Slotkin. Plant Mobile Small RNAs. Cold Spring Harbor Perspectives in Biology / Epigenetics Textbook, Volume 2.
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2013 K. Panda and R. Keith Slotkin. Proposed Mechanism for the Initiation of Transposable Element Silencing by the RDR6-directed DNA Methylation Pathway. Plant Signaling & Behavior v8:e25206.
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2012 G. Martinez-Arias and R. Keith Slotkin. Developmental Reactivation of Transposable Element Silencing in Plants: Functional or Byproduct? Current Opinion in Plant Biology v15 496-502.
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2012 A.D. McCue and R. Keith Slotkin. Transposable Element Small RNAs as Regulators of Gene Expression. Trends in Genetics v28: 616-623.
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2012 F. Borges, R. Gardner, T. Lopes, J.P. Calarco, L.C. Boavida, R. Keith Slotkin, R.A Martienssen, and J.D. Becker. FACS-based Purification of Arabidopsis Microspores, Sperm Cells and Vegetative Nuclei. Plant Methods v8: 44.
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2012 A.D. McCue, S. Nuthikattu, S.H. Reeder and R. Keith Slotkin. Gene Expression and Stress Response Mediated by the Epigenetic Regulation of a Transposable Element Small RNA. PLoS Genetics v8: e1002474
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2012 R. Keith Slotkin, Saivageethi Nuthikattu, and Ning Jiang. The Evolutionary Impact of Transposable Elements on Gene and Genome Regulation. In Molecular Biology and Evolution of the Plant Genome. Eds. Johann Greilhuber and Jonathan Wendel. Springer Press, p35-58.
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2011 Damon Lisch and R. Keith Slotkin. Strategies for Silencing and Escape: The Ancient Struggle Between Transposable Elements and Their Hosts. International Review of Cell and Molecular Biology v292: 119-152.
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2011 A.D. McCue, M. Cresti, J.A. Feijo and R. Keith Slotkin. Cytoplasmic connection of sperm cells to the pollen vegetative nucleus: the functional role of the male germ unit revisited. Journal of Experimental Botany v62: 1621-1631.
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2011 Filipe Borges, Patricia A. Pereira, R. Keith Slotkin, Robert A. Martienssen and Jorg D. Becker. MicroRNA activity in the Arabidopsis male germline. Journal of Experimental Botany v62: 1611-1620.
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2011 N. Jiang, A.A. Ferguson, R. Keith Slotkin and Damon 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 R. Keith Slotkin. The Epigenetic Control of the Athila family of Retrotransposons in Arabidopsis. Epigenetics v5:483-490.
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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 Non-Cell Autonomous Small RNA Pathway in Arabidopsis. Nature v464:628-632.
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2009 R. Keith Slotkin, Mathew Vaughn, Milos Tanurdzic, Filipe Borges, Jorg Becker, Jose Feijo and Robert Martienssen. Epigenetic reprogramming and small RNA silencing of transposable elements in pollen. Cell v136:461-472.
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2009 Kousuke Hanada, Veronica Vallejo, Kan Nobuta, R. Keith Slotkin, Damon Lisch, Blake Meyers, Shin-Han Shiu and Ning Jiang. Expression and Functional Indication of Pack-MULEs in Rice. The Plant Cell v21:25-38.
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2009 R. A. Martienssen, A. Kloc, R. Keith Slotkin and Milos Tanurdzic. Epigenetic Inheritance and Reprogramming in Plants and Fission Yeast. Cold Spring Harbor Symposium on Quantitative Biology, v73:265-271.
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2008 Milos Tanurdzic, Matthew Vaughn, H. Jiang, T.-J. Lee, R. Keith Slotkin, B. Sosinski, William F. Thompson, Rebecca F. Doerge and Robert A. Martienssen. Epigenomic Consequences of Immortalized Plant Cell Suspension Culture. PLoS Biology v6:e302.
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2008 Eyal Gruntman*, YiJun Qi*, R. Keith Slotkin*, Ted Roeder, Robert Martienssen and Ravi Sachidanandam. Kismeth: Analyzer of Plant Methylation States Through Bisulfite Sequencing. BMC Bioinformatics v9:e371. *These authors contributed equally to this manuscript
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2007 R. Keith Slotkin and Robert A. Martienssen. Transposable elements and the epigenetic regulation of the genome. Nature Reviews Genetics v8:272-285.
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2005 R. Keith Slotkin, Michael Freeling and Damon Lisch. Heritable transposon silencing initiated by a naturally occurring transposon inverted duplication. Nature Genetics v37:641-644.
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2003 R. Keith Slotkin, Michael Freeling and Damon Lisch. Mu killer causes the heritable inactivation of the Mutator family of transposable elements in Zea mays. Genetics v165:781-797.
Grants, Fellowships and Awards
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2014-2018
NSF Integrative Organismal Systems, Plant Genome Research Project (Co-PI):
Title: "Genetic and Epigenetic Regulation of Gametophyte Development and Transposon Expression in Maize” -
2013-2018
NSF CAREER Grant, Molecular and Cellular Biosciences, Genetic Mechanisms.
Title: “The Mechanism and Genome-Wide Regulation of Genes and Transposable Elements by Epigenetically Active Small Interfering RNAs”
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2013 Kavli Fellow, US National Academy of Sciences
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2010 Early Career Award from the American Society of Plant Biologists
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2010-2013
NSF Molecular and Cellular Biosciences, Genes and Genome Systems Cluster.
Title: “Defining the role of nurse cells in the propagation of transposable element epigenetic silencing”
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2006-2009 NIH Post-Doctoral Fellowship.
Title: “Transposable element reactivation and influence on gene regulation”
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2005 Teaching Effectiveness Award for essay entitled “Designing a Better Laboratory Course”, GSI Teaching and Resource Center, University of California Berkeley