Hierarchical Differentiation of Myeloid Progenitors Is Encoded in the Transcription Factor Network (original) (raw)
Figure 2
Functional modules in the network.
(A) The GATA-2, GATA-1, FOG-1 regulatory circuit consists of a coherent inhibitory feed-forward loop (GATA-1 and FOG-1 towards GATA-2), an autoregulation (by GATA-1) and a negative feedback (GATA-2 onto itself). The corresponding Boolean update rules and a schematic of the Boolean dynamics is shown on the right, demonstrating how the system is pushed towards maturation. GATA-2 activates its downstream target GATA-1, which synergizes with its cofactor FOG-1 to downregulate GATA-2. Due to the autoregulatory loop, GATA-1 can sustain its expression after its upstream regulator is inhibited. (B) Asymmetric activation of EgrNab and Gfi-1. The gene switch is driven by an upstream feed-forward loop around C/EBP and PU.1. The Boolean update rules between the four players and two possible system trajectories are shown on the right. C/EBP
initially activates PU.1, but can also upregulate its antagonist Gfi-1 which then inhibits the PU.1 target EgrNab. Note that the two stable states - one where EgrNab is finally activated and one where Gfi-1 is activated - are mutually exclusive.