A report published in Nature Immunology provides clues about how certain T cell leukemias arise. The findings show how entire suites of genes can be switched on or off through the interactions of two chromatin binding proteins.
Katia Georgopoulos and colleagues previously showed that T cell leukemias frequently arise in mice lacking the transcription factor Ikaros, but how Ikaros suppressed leukemic transformation was unclear. They now show Ikaros restricts the activity of the chromatin remodeling protein Mi-2beta by comparing their genome-wide binding patterns in wild-type and mutant T cells.
During normal T cell development in the thymus, Ikaros recruits Mi-2beta to genes that direct T lymphocyte differentiation. At the same time, Ikaros tethering of Mi-2beta prevents its recruitment to genes that promote cell growth and division, hence ensuring that their expression remains low. The team notes that Ikaros-deficient cells show a redistribution of Mi-2beta binding to the proliferation-promoting genes, leading to their higher expression, and arrest of T cell development. They conclude that Ikaros harnesses Mi-2beta to a developmental program that also prevents runaway proliferation and leukemic transformation.