The evolutionarily conserved upstream enhancer of the CEBPA gene binds RUNX1, SPI1 (PU.1), GATA2, TAL1 (SCL), FLI1, and MYB in hemopoietic progenitor cells and myeloid progenitor cells (inferred from mouse). Unlike the promoter of the mouse Cebpa gene, the human CEBPA promoter does not bind CEBPA and autoregulation of CEBPA occurs indirectly through CEBPA-stimulated binding of USF to the promoter of the CEBPA gene (Timchenko et al. 1995). As inferred from mouse homologs, RUNX1, GATA2, SCL, SPI1, and FLI1 bind concomitantly.
RUNX1, SPI1 (PU.1), GATA2, TAL1 (SCL), MYB, and CEBPA itself all contribute to the level of transcription of CEBPA in hemopoietic progenitor cells and myeloid progenitor cells (inferred from mouse homologs). High levels of CEBPA appear to favor CEBPA:CEBPA homodimers and lead to granulopoiesis; low levels of CEBPA appear to favor CEBPA:AP-1 heterodimers and lead to monopoiesis. LEF1 also directly activates transcription of CEBPA (Skokowa et al. 2006, Skokowa et al. 2012), but appears to act at the transition of granulocyte-macrophage precursors to promyelocytes, a later stage of granulopoiesis. The relative levels of SPI1 (PU.1) and CEBPA (SPI1 to CEBPA mRNA expression ratio) in granulocytic–macrophage progenitors have been suggested to regulate monocyte versus neutrophil cell-fate choice (Dahl et al. 2003).
RUNX1, in complex with CBFB, binds to the core TAL1 complex consisting of TAL1 (SCL), TCF3 (E2A) or TCF12 (HEB), LMO1 or LMO2, LDB1 and GATA1, GATA2 or GATA3 (Wilson et al. 2010, Tijssen et al. 2011, Sanda et al. 2012, Mansour et al. 2014, Hoang et al. 2016). Assembly of the RUNX1- and GATA3-containing TAL1 complex is positively regulated by the CDK7-containing CAK complex (Kwiatkowski et al. 2014).