Growth factor independence 1 (Gfi1) as a regulator of lymphocyte development and activation

T- and B-lymphocytes are important elements in the immune defense repertoire of higher organisms. The development and function of lymphoid cells is regulated at many levels one being the control of gene expression by transcription factors. The zinc finger transcriptional repressor Gfi1 has emerged as a factor that is critically implicated in the commitment of precursor cells for the lymphoid lineage. In addition, Gfi1 controls distinct stages of early T- or B-lymphoid development and is also critical for their maturation, activation and effector function. From many years of work, a picture emerges in which Gfi1 is part of a complicated, but well orchestrated network of interdependent regulators, most of which impinge on lymphoid development and activation by transcriptional regulation. Biochemical studies show that Gfi1 is part of a large DNA binding multi-protein complex that enables histone modifications, but may also control alternative pre mRNA splicing. Many insights into the biological role of Gfi1 have been gained through the study of gene deficient mice that have defects in B- and T-cell differentiation, in T-cell selection and polarization processes and in the response of mature B- and T-cells towards antigen. Most importantly, the defects seen in Gfi1 deficient mice also point to roles of Gfi1 in diseases of the immune system that involve auto-immune responses and acute lymphoid leukemia and lymphoma. (C) 2011 Elsevier Ltd. All rights reserved.