Jackson Laboratory Researchers Find Mechanisms for Generating Genetic Diversity from Egg to Embryo

Date: October 12, 2004

Bar Harbor, Maine - A Jackson Laboratory research team has shed light on events orchestrating the changes when mammalian eggs  are fertilized and become embryos. The researchers, led by Senior Staff Scientist Barbara Knowles, have discovered that expression of genes in mouse eggs and very early embryos is activated in part by controlling elements of retroviruses. These viruses, called retrotransposons, have the ability to propagate and insert themselves into different positions within the genome.

The research, published as the featured article in October issue of Developmental Cell, suggests that retrotransposons may not be just the "junk DNA" once thought, but rather appear to be a large repository for start sites for gene expression. Therefore, more than one third of the mouse and human genomes, thought to be non-functional, may play some role in the regulation gene expression.

Dr. Knowles and colleagues from The Jackson Laboratory found that distinct retrotransposon types are unexpectedly active in mouse eggs, and others are activated in early embryos. Surprisingly, by acting as alternative promoters, retrotransposon-derived controlling elements drive the coordinated expression of multiple mouse genes. "To our knowledge, this is the first report that such elements can initiate synchronous, developmentally regulated expression of multiple genes", says Dr. Knowles. "Also, random insertions of these elements can introduce variation in genes, potentially altering their function".

The researchers, including Jackson colleagues Anne E. Peaston (currently at the University of Sydney), Alexei V. Evsikov, Joel H. Graber, Wilhelmine N. de Vries, Andrea E. Holbrook, and Adjunct Senior Staff Scientist Davor Solter of the Max Planck Institute for Immunobiology in Freiburg, Germany, believe that expression of retrotransposons during very early stages of development may contribute to the reprogramming of the mammalian embryonic genome by activating mechanisms to inhibit their own replication.

The independent, nonprofit Jackson Laboratory, founded in 1929, is the world's largest mammalian genetics research facility. The Laboratory is also the source of more than 2,800 stocks and strains of genetically defined mice, the home of the Mouse Genome Database and many other publicly available information resources, and an international hub for scientific courses, conferences, training and education.

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Peaston AE, Evsikov AV, Graber JH, de Vries WN, Holbrook AE, Solter D, and Knowles BB: Retrotransposons Regulate Host Genes in Mouse Oocytes and Preimplantation Embryos. Developmental Cell, Vol 7, 597-606, October 2004.

Contact(s): Joyce Peterson, The Jackson Laboratory, 207-288-6058

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