Fig. 7

Validation of the molecular interactions by sequence analysis. a According to our survey of gene sequences, p18 does not harbor the direct recognition element (i.e. binding motif) of Maff in its transcription promoter region; therefore, we check if there is any intermediate that both contains that motif (in the promoter region) and can negatively regulate p18. We have found that Blimp1/Prdm1, which is also a transcription factor in the regulation of hematopoietic differentiation, harbors the Maff binding motif in its promoter region; and the motif is 156 bp upstream the transcription start site (TSS). Meanwhile, Blimp1/Prdm1 can transcriptionally repress p18 in regulation of the cycling of hematopoietic cells. Thus the transcription regulatory relation “Maff ― → Blimp1 − ⊣ p18” is indicated, and our computational inference “Maff − ⊣ p18” is well supported. b Our survey has also identified that Anapc11, which is a core coding gene of the anaphase-promoting complex/cyclosome (APC/C) that inhibits mitotic cyclins and greatly suppresses G0 → G1/G1 → S, links to the cis element that Egr3 recognizes and exerts transcription activation (523 bp upstream the TSS). Therefore, it implies that “Egr3 ― → Anapc11” and “Anapc11 −⊣ Cyclin D/Cdk4/6, Cyclin E/Cdk2”; thus our computational inference that “Egr3 − ⊣ CyclinD:Cdk4/6, CyclinE:Cdk2” is supported