| GFI1b and its homolog GFI1 are transcriptional repressors and important regulators of erythroid and megakaryocytic development and differentiation. GFI1b negatively regulates transcription by recruiting chromatin regulatory proteins including CoREST, the histone demethylase LSD1 and HDACs 1 and 2, which associate with GFI1b via its SNAG repression domain. GFI1b has also been shown to control the differentiation of erythroid and megakaryocytic progenitors by regulating TGF-β signaling at the bipotent progenitor stage. Inactivation of GFI1b in mice leads to embryonic lethality due to failure to produce functional erythrocytes and megakaryocytes. The GFI1b gene locus can be autoregulated by binding to its own promoter in hematopoietic cells, likely through interacting with GATA-1, another transcription factor essential for erythroid and megakaryocytic development. Mutations in GFI1b are implicated in various leukemias and GFI1b has been found in a complex with GATA-1 and SUZ12 on repressed genes in erythroleukemia cells. |
