A model for developmental regulation of gene expression during erythro-megakaryopoiesis. A stem/progenitor cell-expressed transcription factor “heptad” (GATA2, LYL1, TAL1, ERG, FLI1, RUNX1, and LMO2) binds and transcriptionally primes MEG-specific genes in hematopoietic stem/progenitor cells (HSPCs) (top). Events that occur upon subsequent differentiation of these cells into MEG and ERY are indicated in the middle and bottom panels. Further transcriptional activation of the primed genes in MEG is mediated by GATA switching (replacement of GATA2 by GATA1), ETS factors, and other mechanisms. In most cases, terminal silencing of primed MEG-specific genes in ERY depends on the departure of GATA proteins and MEG-specific transcriptional activators, such as ETS factors, and possible binding of ERY-specific transcriptional repressors. In some instances, terminal repression of MEG-specific genes in ERY appears to be associated with GATA switching and likely relies on recruitment of ERY-specific transcriptional repressors. In addition to the heptad of factors identified in HPC-7 cells (Wilson et al. 2010), the lineage priming “heptad” also likely includes the protein LDB1, which mediates interactions among several of the proteins.
