Master switch

It has long been known that 20 gene regulators control the development of blood cells from blood stem cells in the bone marrow. All these regulators have a common genetic element, called PU.1, which plays a crucial role in regulating blood cell formation. PU.1 guides the development of two major blood cell lines of the immune system, namely the lymphocytes and the myeloid blood cells. It also regulates the blood stem cells' own development thereby ensuring that new blood cells are produced as required. But what was not known was what controlled PU.1.

Now, Frank Rosenbauer from the Max-Delbrck Center for Molecular Medicine, Berlin, has discovered the master switch that controls PU.1 in mice. Called an upstream regulatory element, this master switch not only turns the gene regulator on or off but also tweaks it, thus determining whether B-cells or T-cells develop from lymphocyte progenitor cells. B-cells and T-cells are important components of the immune system. Animals that lack the upstream regulatory element can develop leukaemia and, consequently, can die within a few months. The finding was published on November 27, 2005, in the online version of Nature Genetics.

With respect to the development of T-cells, Rosenbauer and colleagues showed that the switch also plays a crucial role in the healthy development of complex organisms. In case of lack of regulation by this element, malformations or tumours can develop. In case of any disturbance in regulation of PU.1, for instance, if it is not turned off properly, T-cells cannot mature.

The scientists now plan to study the blood of leukaemia patients to test the findings in humans.

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