Patterns of development

For a tiny embryo to grow into a viable fruit fly, mouse, or human, the correct genes in each cell must turn on and off in precisely the right sequence. This intricate molecular dance produces the many parts of the whole creature, from muscles and skin to nerves and blood.

At the most basic level, genes are turned on when an enzyme called RNA polymerase binds to the DNA at the beginning of a gene. The RNA polymerase copies the gene’s DNA into a complementary strand of messenger RNA, which then instructs the cell to make the protein the gene codes for. Several years ago, however, Assistant Investigator Julia Zeitlinger, PhD, made a surprising discovery. The RNA polymerase doesn’t just attach to DNA and start copying. Instead, it binds and then pauses, waiting for another signal before it goes to work. Now, new work by Zeitlinger’s lab has revealed far more about the role of paused RNA polymerase in embryonic development—and turned up yet another surprise.

The team found that the pattern of genes with poised polymerase in muscle and nerve cells varies depending on the stage of development and not on tissue type as expected. To prevent the wrong poised genes from being turned on, so-called polycomb proteins—a family of proteins whose action varies by tissue type—repress poised polymerase.

Together, these two mechanisms explain how genes during the development of both muscle and nerves first can be poised to express at the right time by paused polymerase, and then only activate in the right tissue type. And because the researchers were able to show the same mechanisms at work in human cells, too, the findings could eventually lead to a better understanding of disease.

The study was published in the December 27, 2012, issue of Cell Reports.