Control of Gene Expression Demonstrated

Intervention in the process whereby genes are turned “on” or “off” has been demonstrated by scientists at the Hebrew University-Hadassah Medical School. The work offers promise for future genetic treatment to control undesirable tissue growth, such as in cancer.

The experimental work of the group is described in a recent article in the journal, Nature Genetics. The researchers succeeded in showing how manipulation of the methylation process in animals can turn genes which are normally inactive into active ones.

Early in the development of the embryo in the uterus, a methyl “cap” is attached to most of the genes in the nuclei of the dividing cells, with the exception of those “housekeeping” genes which are present in every cell and are necessary to keep them functioning.

This methylation process prevents the tissue-specific genes (those which produce tissues such as liver, heart, muscle, etc., cells) from expressing themselves (becoming activated) every time there is cell division. Those genes are selectively unmethylated only at various stages and for specific periods, as required, in the normal development process of the organism.

The Hebrew University-Hadassah Medical School scientists were successful in showing that methylation works by affecting chromosome structure. Unmethylated genes remain open and accessible, while methylation causes genes to be packaged in a closed form – explaining why they are inactive. In their experimental work, the scientists were able to artificially “open” or unmethylate certain genes – that is, turn them “on” — and keep them that way for as long as desired.

This can have consequences, for example, in controlling tumorous growths. In the latter stages of cancerous spread, those genes which normally control unwanted cell growth are abnormally shut down. By being able to keep such beneficial genes active, it would be possible to halt the tumors’ progress. Such an achievement, however, has yet to be demonstrated in laboratory experiments.

The authors of the article on methylation and its manipulation are: Howard Cedar, the Harry and Helen L. Brenner Professor of Molecular Biology at the Hebrew University-Hadassah Medical School, together with graduate students Tamar Hashimshony and Jianmin Zhang; senior researcher Dr. Ilana Keshet of the Medical School; and Dr. Michael Bustin of the National Cancer Institute, U.S. National Institutes of Health, in Bethesda. MD.