The Ets transcription factor family (Ets-1, Ets-2, Erg-1-3, Elk-1, Elf-1, Elf-5, NERF, PU.1, PEA3, ERM, FEV, ER8l, Fli-1, TEL, Spi-B, ESE-1, ESE-3A, Net, ABT1 and ERF) are DNA-binding proteins that influence lymphoid development and activity. The Ets family monomeric proteins bind the consensus DNA site GGA(A/T) through a unique winged helix-turn-helix motif known as the Ets domain. PU.1 (Spi-1/Spi-A), Spi-B and Spi-C are closely related Ets family members which share a conserved divergent sequence within the Ets domain that enables their binding to the non-canonical AGAA sites. PU.1 transactivates a large number of B cell genes, such as those encoding CD72, CD20 and Btk, and Spi-B enhances expression of many of these same target genes. PU.1 is expressed in a wide variety of hematopoetic cells, including B cells, early T-cells, megakaryocytes, granulocytes, mast cells, immature erythrocytes and myeloid cells. Alternatively, Spi-B expression is limited to B cells and immature T cells, where expression accumulates through T-lineage commitment and then is dramatically absent following the beta-selection checkpoint.
