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Changing Epigenetic Modifications That Enable Transposons To Run Amok

Date:
December 10, 2008
Source:
Cold Spring Harbor Laboratory
Summary:
Changes in gene activity allow cells to cope with environmental changes but leave genes prone to mis-regulation by transposons -- bits of DNA that jump around the genome, often disrupting normal gene function. A host of 'epigenetic' mechanisms normally prevents such genomic chaos. By mapping the changing epigenetic landscape of continuously dividing cells, scientists have now captured the epigenetic alterations and the molecular players that allow transposons to run amok.

Much like cancer cells, plant cells grown for a long time outside of their normal milieu, in culture dishes, have highly unstable genomes. Changes in gene activity, or how genes are "expressed," help cells cope with challenging culture conditions but inadvertently also leave genes prone to mis-regulation by transposons -- bits of DNA that can jump around in the genome, inserting themselves into random genetic locations, often disrupting normal gene function and regulation.

Such genomic chaos, found in cancer and other diseases, is normally prevented by a host of mechanisms that scientists call epigenetic: they modify the expression of genes, although not by causing mutations in the sequence of the genome's DNA "letters."

How transposons (sometimes called mobile genetic elements) escape these controls is one of the questions driving the research of Professor Robert Martienssen -- a pioneer of plant epigenetics -- at Cold Spring Harbor Laboratory (CSHL). By undertaking the ambitious task of mapping the changing epigenetic landscape of continuously dividing plant cells, Martienssen's team has succeeded in capturing in detail epigenetic alterations and the molecular players that allow transposons to run amok.

Shifting RNA patterns

The numerous and diverse transposons present within the plant genome are normally rendered inactive by a series of complicated steps masterminded by small molecules of RNA, called small interfering RNA (siRNA). They perform this feat in a phenomenon known as RNA interference (RNAi). The discovery that modifications of heterochromatin -- densely packed, genetically "inactive" regions of DNA -- are targeted by RNAi was made by Martienssen's team in yeast cells and heralded as one of the leading scientific breakthroughs of 2002.

Martienssen's team now has found that in immortalized cells -- cells that are coaxed to grow endlessly in culture dishes -- the epigenetic changes resulting in a loss of heterochromatin and transposon "re-activation" are not due to a loss of the proteins that regulate heterochromatin. Instead, they find that the epigenetic modifications are due to a change in the population of siRNAs produced in the continuously dividing cells. When this occurs in the vicinity of genes, this epigenetic control can have important consequences for the organism. According to Martienssen, "our work implicates RNAi in epigenetic chromatin changes that occur in immortalized cells."

Epigenetic "restructuring" by siRNA

The CSHL researchers find that transposons that have lost heterochromatic marks are no longer associated with siRNA that are 24 nucleotides, or RNA "letters," in length. Rather, these re-activated transposons become associated with siRNAs that are 21nucleotides in length. In contrast, the transposons that retain their original heterochromatic marks and therefore remain silent continue to stay associated with 24-nucleotide siRNAs.

The team's eventual goal is to understand the mechanism responsible for the creation of epialleles – epigenetic variations in gene expression patterns that stem from the creation of particular chromatin states. These predispose particular genes to become active when they shouldn't be and shut off the activity of genes that are essential. The team's epigenetic profiling study now implicates siRNA-driven heterochromatin restructuring as a mechanism that might lead to epiallele formation.


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. Tanurdzic et al. Epigenomic Consequences of Immortalized Plant Cell Suspension Culture. PLoS Biology, 2008; 6 (12): e302 DOI: 10.1371/journal.pbio.0060302

Cite This Page:

Cold Spring Harbor Laboratory. "Changing Epigenetic Modifications That Enable Transposons To Run Amok." ScienceDaily. ScienceDaily, 10 December 2008. <www.sciencedaily.com/releases/2008/12/081210143412.htm>.
Cold Spring Harbor Laboratory. (2008, December 10). Changing Epigenetic Modifications That Enable Transposons To Run Amok. ScienceDaily. Retrieved April 24, 2014 from www.sciencedaily.com/releases/2008/12/081210143412.htm
Cold Spring Harbor Laboratory. "Changing Epigenetic Modifications That Enable Transposons To Run Amok." ScienceDaily. www.sciencedaily.com/releases/2008/12/081210143412.htm (accessed April 24, 2014).

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