Distinct Mechanisms Control Transposon Inheritance through Overlapping Pathways

Distinct Mechanisms Control Transposon Inheritance through Overlapping Pathways

  • Published: December 22, 2003
  • DOI: 10.1371/journal.pbio.0000084

When Barbara McClintock discovered transposable genetic elements in maize in the early 1950s at Cold Spring Harbor Laboratory (CSHL) in New York, she dubbed them “controlling elements,” since their manner of jumping from one chromosomal site to another controlled their own function as well as that of nearby genes. Just as genetic material is transferred from “parent” to “daughter” cell, these changes in “transposon” activity, and corresponding changes in gene function, are inherited by cellular progeny. The significance of McClintock's jumping genes was not widely recognized at first, but transposable elements are now considered a classical model for epigenetic inheritance—the study of heritable changes in gene expression and regulation that arise independently of changes in DNA sequence.

Transposons are normally “silent”—that is, inactive and stationary—but various mechanisms can rouse them and thus influence their regulation of gene expression. They can be inherited in this active state. Because hyperactive transposons would cause genetic chaos—cancer and other diseases arise from misplaced genes—epigenetic controls are crucial. A process called DNA methylation is thought to keep transposons from running amok, but other mechanisms that affect epigenetic inheritance may also play a role. While the molecular basis of these regulatory pathways is not clear, it is apparent that they interact. Investigating the nature and consequences of these interactions, Rob Martienssen and his colleagues at CSHL found that different transposons respond to different types of epigenetic regulation and identified two distinct mechanisms of transposon silencing that likely interact in a common pathway.

The challenge of teasing out the individual contributions of these highly complex, overlapping regulatory pathways is complicated by the fact that few model organisms suit the task. Fission yeast, the organism of choice for many fundamental cell biology investigations, seems to lack DNA methylation, while mice can't live without it, ruling them out as viable subjects for experiments that disturb this form of DNA modification. The Arabidopsis thaliana plant, on the other hand, not only can survive such disturbances but can also produce offspring ripe for studying epigenetic inheritance patterns. Plus, this plant has already helped researchers identify many genes involved in epigenetic regulation.

To study the molecular basis of epigenetic inheritance and the interaction of the various regulatory networks—DNA methylation, histone modification, and RNA interference—Martienssen et al. used several Arabidopsis strains with mutations known to affect these processes as well as the epigenetic inheritance of active transposons. DNA methylation chemically modifies DNA; histone proteins are modified by other molecules and alter chromatin structure (the complex of DNA and proteins that packages DNA in cells); and RNA interference (RNAi) blocks DNA transcription. Focusing on a representative group of transposons, Martienssen et al. crossed mutants in DNA methylation, histone modification, and chromatin remodeling with nonmutant plants and characterized the impacts on each transposon.

Using transposon expression (transposons must be expressed to jump around) in the offspring to determine whether transposable elements were silent, transiently activated, or heritably activated, the researchers found that when each of the transposons were subjected to the same mutations, they did not all respond in the same way. While some mutations affected all of the elements, other mutations affected only a subset. The quality of the responses also varied; some mutations caused changes that were transient, that is, lost in the next generation, while others were inherited.

They also found that RNAi, which silences transposable elements in fruitflies (Drosophila) and worms (Caenorhabditis elegans), influences epigenetic inheritance. Small interfering RNA (siRNA), however, somehow interacts with other pathways, such as DNA methylation and chromatin remodeling, to do so.

Martienssen et al. say these results indicate that transposons differ in their pattern of regulation and tend to respond to different types of epigenetic regulation, suggesting there are distinct mechanisms of transposon silencing but that the mechanisms or pathways probably interact. Given the potentially damaging effects of transposition and its seemingly ubiquitous presence in living things, it's reasonable to wonder whether transposable elements evolved as a flexible response to special circumstances, like environmental stress, a possibility proposed by McClintock. The epigenetic mechanisms that control these elements are vital in regulating the structure and organization of the genome and in establishing the right balance between genetic variation and fidelity, the molecular foundation of evolution. It seems only fitting that biologists at Cold Spring Harbor would continue to plumb the implications of McClintock's work—and that their model system of choice would be a plant.

Jumping genes discovered in maize through their effect on kernel pigmentation