R. Keith Slotkin

R. Keith Slotkin
Associate Professor of Biological Sciences; Principal Investigator, Donald Danforth Plant Science Center
Donald Danforth Plant Science Center

PhD, 2005 University of California, Berkeley

Research Summary

Determining how transposable elements become epigenetically silenced

Research Description

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.

Awards and Honors

Kavli Frontiers of Science Fellow, U.S. National Academy of Science 2013

Early Career Award, American Society of Plant Biologists 2010

Selected Publications

See Google Scholar for a list of Dr. Slotkin's publications.