Researchers Show How Basic Biology Understanding Can Further Genetic Engineering

A step to further understanding of the process whereby genes are turned on and off in living organisms has been achieved by a team of researchers at the Hebrew University-Hadassah Medical School. Understanding of this process has substantial consequences for furthering the use of medical genetic engineering to grow new tissue to replace damaged or defective organs or to halt the growth of undesirable tumors.

The achievement is described in an article in the current issue of Nature magazine, written by Howard Cedar, the Harry and Helen L. Brenner Professor of Molecular Biology at the Medical School, together with Jianmin Zhang, Xu Feng, both graduate students from China; graduate student Tamar Hashimshony; and senior researcher Dr. Ilana Keshet. The article is entitled “Establishment of Transcriptional Competence in Early and late S-Phase.”

Generally speaking, said Prof. Cedar, a winner of the Israel Prize in biology, there are two kinds of genes in every cell—those which control the “housekeeping” duties which are necessary to keep all cells functioning, and specific genes which give each tissue its unique properties.

Since a complete set of genes exists in every cell, no matter where it is located in a given organism, most tissue specific genes are actually in a dormant (unexpressed) state. Only those tissue specific genes needed for a particular cell type (liver, heart, brain, etc.) are activated along with the housekeeping genes.

How are some genes kept on while others are turned off? The new studies from Prof. Cedar’s laboratory suggest that this occurs during the process of gene duplication that takes place prior to cell division. Housekeeping genes get copied early during a unique “window of opportunity” which makes them active, while other genes are copied later, and as a result are mostly doomed to inactivity. Thus, in a sense, each cell knows how to pass on to the next generation both the genes themselves, as well as the instructions for setting up their state of activity or inactivity. This concept was actually suggested 25 years ago, but the Hebrew University-Hadassah researchers are the first to prove it.

These new findings provide fundamental information important for understanding how the embryo develops and for deciphering the genetic defects in cancer. This will also help scientists develop better methods for therapeutic genetic engineering by providing the technology required to insure that when genes are inserted they will always be active.