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. 2011 Jul;31(14):2817–2826. doi: 10.1128/MCB.01305-10

Fig. 5.

Fig. 5.

(A) Schematic diagrams showing Runx1-Smad6 interactions. Smad6 and Runx1 are targets of Bmp4 signaling and are independently regulated by the Fli1-Gata2-Scl triad. Components of the triad stabilize the Smad6-Runx1 rheostat by facilitating Runx1 binding to the Smad6-57 enhancer. (B) Runx1 ChIP enrichments in HPC-7 cells transduced with either an Scl knockdown (shScl) or control (shluc) vector. Runx1 enrichment ratios at the Smad6-57 and Runx1+23 enhancers are reversed following Scl knockdown and are unchanged at the control region (Afp promoter). The ratios of Runx1 binding at the Smad6-57, Runx1+23, and Afp regulatory regions in control (shluc) HPC-7 cells are 18, 8, and 1, respectively. The ratios of Runx1 binding at these regions in shScl HPC-7 cells (∼50% Scl mRNA) are 4.5, 11, and 1, respectively. (C) Perturbation of the Runx1-Smad6 rheostat by proteasome inhibition. (i) A schematic showing Smurf1-mediated targeting of the Smad6-Runx1 complex to the proteasome. (ii) MG132 interrupts the degradation of Runx1 by inhibiting the proteasome, which leads to the increased expression of both Smad6 and Runx1. (iii) The increase in Smad6 and Runx1 gene expression is associated with increased Runx1 binding at both the Smad6 and Runx1 gene promoters. **, P < 0.01; ***, P < 0.001.