The Gene Control Hierarchy

About 90% of the mutations that cause disease occur in short regulatory segments of the genome that sit next to the genes and determine whether a particular gene will be turned on, where and how strongly.
 

A research team led by Dr. Ido Amit of the Weizmann Institute Immunology Department, together with scientists from the Broad Institute in Massachusetts, including Manuel Garber, Nir Yosef and Aviv Regev, and Nir Friedman of the Hebrew University of Jerusalem, developed an advanced, automated system for mapping these sites, and then used it to uncover important principles of how these regulatory elements function. This system enabled a small team of researchers to produce results that rival the efforts of huge scientific consortiums, in a relatively short period of time.

Among other things, their study, which appeared recently in Molecular Cell, revealed that the actions of these regulatory factors can be neatly classified into three levels in a sort of regulatory hierarchy. In the bottom tier are those factors that create the rough divisions into main cell types by directing cell differentiation. These factors are the “basic identity” guides that can, on their own, determine whether a cell will have the characteristics of a muscle cell, a nerve cell, etc. On the second tier are the regulatory factors that determine a cell’s sub-identity, which they do by controlling the strength of a gene’s expression. These factors are in charge of producing closely-related sub-types, for instance, muscle fibers that are either smooth or striated, or closely-related immune cells. Regulatory factors in the third tier are even more specialized: They only affect the expression of certain genes that are called into action in response to signals from outside the cell: bacterial invasion, hormones, hunger pangs, etc.

Amit: “The new method for mapping the gene’s regulatory plan may open new vistas for investigating all sorts of biological processes, including the system failures that occur in disease.”

 

Dr. Ido Amit's research is supported by the Abramson Family Center for Young Scientists; the Abisch Frenkel Foundation for the Promotion of Life Sciences; Sam Revusky, Canada; the Leona M. and Harry B. Helmsley Charitable Trust; the M.D. Moross Institute for Cancer Research; Drs. Herbert and Esther Hecht, Beverly Hills, CA; the estate of Ernst and Anni Deutsch; and the estate of Irwin Mandel.